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Sample records for intradermal infection model

  1. PREVALENCE OF PARACOCCIDIOIDOMYCOSIS INFECTION BY INTRADERMAL REACTION IN RURAL AREAS IN ALFENAS, MINAS GERAIS, BRAZIL

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    Evandro Monteiro de Sá Magalhães

    2014-07-01

    Full Text Available This study aimed to estimate the prevalence of paracoccidioidal infection by intradermal reaction (Delayed-Type Hypersensitivity, DTH to Paracoccidioides brasiliensis in rural areas in Alfenas, Southern Minas Gerais (MG State, Brazil, and to assess risk factors (gender, occupation, age, alcohol intake and smoking associated with infection. We conducted a population-based cross-sectional study using intradermal tests with gp 43 paracoccidioidin in 542 participants, who were previously contacted by local health agents and so spontaneously attended the test. Participants underwent an interview by filling out a registration form with epidemiological data and were tested with an intradermal administration of 0.1 mL of paracoccidioidin in the left forearm. The test was read 48 hours after injection and was considered positive if induration was greater than or equal to 5 mm. Out of 542 participants, 46.67% were positive to the skin test. Prevalence increased in accordance with an increase of age. There was statistical significance only for males. Occupation, alcohol intake and smoking habits were not significantly associated with the risk of paracoccidioidomycosis infection. There is relevance of paracoccidioidomycosis infection in such rural areas, which suggests that further epidemiological and clinical studies on this mycosis should be done in the southern part of Minas Gerais State.

  2. Prevalence of paracoccidioidomycosis infection by intradermal reaction in rural areas in Alfenas, Minas Gerais, Brazil.

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    Magalhães, Evandro Monteiro de Sá; Ribeiro, Carla de Fátima; Dâmaso, Carla Silva; Coelho, Luiz Felipe Leomil; Silva, Roberta Ribeiro; Ferreira, Eric Batista; Rodrigues, Maria Rita; Camargo, Zoilo Pires de; Velloso, Tânia Regina Grão; Malaquias, Luiz Cosme Cotta

    2014-01-01

    This study aimed to estimate the prevalence of paracoccidioidal infection by intradermal reaction (Delayed-Type Hypersensitivity, DTH) to Paracoccidioides brasiliensis in rural areas in Alfenas, Southern Minas Gerais (MG) State, Brazil, and to assess risk factors (gender, occupation, age, alcohol intake and smoking) associated with infection. We conducted a population-based cross-sectional study using intradermal tests with gp 43 paracoccidioidin in 542 participants, who were previously contacted by local health agents and so spontaneously attended the test. Participants underwent an interview by filling out a registration form with epidemiological data and were tested with an intradermal administration of 0.1 mL of paracoccidioidin in the left forearm. The test was read 48 hours after injection and was considered positive if induration was greater than or equal to 5 mm. Out of 542 participants, 46.67% were positive to the skin test. Prevalence increased in accordance with an increase of age. There was statistical significance only for males. Occupation, alcohol intake and smoking habits were not significantly associated with the risk of paracoccidioidomycosis infection. There is relevance of paracoccidioidomycosis infection in such rural areas, which suggests that further epidemiological and clinical studies on this mycosis should be done in the southern part of Minas Gerais State.

  3. Intradermal tuberculin testing of wild African lions (Panthera leo) naturally exposed to infection with Mycobacterium bovis.

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    Keet, D F; Michel, A L; Bengis, R G; Becker, P; van Dyk, D S; van Vuuren, M; Rutten, V P M G; Penzhorn, B L

    2010-08-26

    African lions in the southern half of Kruger National Park (KNP) are infected with Mycobacterium bovis. Historically, reliable detection of mycobacteriosis in lions was limited to necropsy and microbiological analysis of lesion material collected from emaciated and ailing or repeat-offender lions. We report on a method of cervical intradermal tuberculin testing of lions and its interpretation capable of identifying natural exposure to M. bovis. Infected lions (n=52/95) were identified by detailed necropsy and mycobacterial culture. A large proportion of these confirmed infected lions (45/52) showed distinct responses to bovine tuberculin purified protein derivative (PPD) while responses to avian tuberculin PPD were variable and smaller. Confirmed uninfected lions from non-infected areas (n=11) responded variably to avian tuberculin PPD only. Various non-tuberculous mycobacteria (NTM) were cultured from 45/95 lions examined, of which 21/45 were co-infected with M. bovis. Co-infection with M. bovis and NTM did not influence skin reactions to bovine tuberculin PPD. Avian tuberculin PPD skin reactions were larger in M. bovis-infected lions compared to uninfected ones. Since NTM co-infections are likely to influence the outcome of skin testing, stricter test interpretation criteria were applied. When test data of bovine tuberculin PPD tests were considered on their own, as for a single skin test, sensitivity increased (80.8-86.5%) but false positive rate for true negatives (18.75%) remained unchanged. Finally, the adapted skin test procedure was shown not to be impeded by persistent Feline Immunodeficiency Virus(Ple) co-infection. Copyright 2010 Elsevier B.V. All rights reserved.

  4. The use of serological tests in combination with the intradermal tuberculin test maximizes the detection of tuberculosis infected goats.

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    Bezos, Javier; Roy, Álvaro; Infantes-Lorenzo, José Antonio; González, Isabel; Venteo, Ángel; Romero, Beatriz; Grau, Anna; Mínguez, Olga; Domínguez, Lucas; de Juan, Lucía

    2018-05-01

    The diagnosis of tuberculosis (TB) in goats is based mainly on the single and comparative intradermal tuberculin (SIT and CIT) tests and, exceptionally, on the interferon-gamma (IFN-γ) assay, however they are not perfect in terms of sensitivity and specificity. Nevertheless, various serological assays that provide a potential cost-effective approach for the control of TB are also available or under development, and a variety of results have been reported regarding the ability of these tests to detect infected animals, particularly in the early stages of infection. In the present study, SIT/CIT and IFN-γ tests and three different serological assays were evaluated during two consecutive herd testing events in a recently infected caprine herd (n = 447) with a high prevalence of infection in order to evaluate their performance and provide field data with which to improve the TB control programs in this species. The proportion of infected animals that tested positive among all the infected goats (T+/I+ value) in the last herd testing event ranged from 26.2% (IC95%; 19.3-34.5) to 85.7% (IC95%; 78.5-90.7) using cell-based diagnostic tests. The SIT/SCIT tests detected more infected goats than the IFN-γ test, regardless of the interpretation criteria. The T+/I+ value of serology was 83.2 (IC95%; 75.2-89), although it increased significantly (P < 0.05) when using samples collected 15 days after the intradermal test (100%, IC95%; 97-100). In general, a parallel interpretation of intradermal tests with serology maximized the detection of infected goats. These results demonstrate that serological tests are valuable diagnostic tools to maximize the detection of TB infected goats, even in recent outbreaks, accelerating the eradication process. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. The mouse intradermal test, a well-established and reliable model in skin tolerance testing.

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    Gloxhuber, C; Kästner, W

    1985-02-01

    The intradermal test in mice is a valuable model for assessing dermal tolerance to chemical substances. The test material is administered intracutaneously to hairless or depilated mice through a fine syringe, the animals are killed after 24 hours and the treated skin is removed, dried and assessed for reaction area, erythema and oedema. The skin fragments can be preserved as a record of the findings. While direct transfer of the findings from mouse to man is likely to be misleading, the test is well suited to comparative studies. Moreover it requires only small numbers of mice.

  6. Intradermal capsaicin as a neuropathic pain model in patients with unilateral sciatica

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    Aykanat, Verna; Gentgall, Melanie; Briggs, Nancy; Williams, Desmond; Yap, Sharon; Rolan, Paul

    2012-01-01

    AIM This study compared the responses between patients with unilateral sciatica and pain-free volunteers following administration of intradermal capsaicin. METHODS Fourteen patients with unilateral sciatica and 12 pain-free volunteers received one injection per hour over 4 h of 1 µg and 10 µg capsaicin, into each calf. For each dose, spontaneous pain (10 cm VAS), area of flare (cm2) and the sum of allodynia and hyperalgesia radii across eight axes (cm) were recorded pre-injection and at 5, 15, 30, 45 and 60 min post injection. RESULTS Sciatica subjects experienced higher spontaneous pain and hyperalgesia responses in both legs compared with pain-free volunteers. The largest mean difference in spontaneous pain was 2.8 cm (95% CI 1.6, 3.9) at 5 min in the unaffected leg following 10 µg. The largest mean difference in hyperalgesia was 19.7 cm (95% CI 12.4, 27.0) at 60 min in the unaffected leg following 10 µg. Allodynia was greater in patients than in controls with the largest mean difference of 2.9 cm (95% CI 1, 4.8) at 5 min following 10 µg in the affected leg. Allodynia was also higher in the affected leg compared with the unaffected leg in sciatica patients with the highest mean difference of 3.0 cm (95% CI 1.2, 4.7) at 5 min following 10 µg. CONCLUSIONS The responses to intradermal capsaicin are quantitatively and qualitatively different in unilateral sciatica patients compared with pain-free controls. PMID:21740458

  7. Intradermal delivery of vaccines: potential benefits and current challenges

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    Hickling, JK; Jones, KR; Friede, M; Chen, D; Kristensen, D

    2011-01-01

    Abstract Delivery of vaccine antigens to the dermis and/or epidermis of human skin (i.e. intradermal delivery) might be more efficient than injection into the muscle or subcutaneous tissue, thereby reducing the volumes of antigen. This is known as dose-sparing and has been demonstrated in clinical trials with some, but not all, vaccines. Dose-sparing could be beneficial to immunization programmes by potentially reducing the costs of purchase, distribution and storage of vaccines; increasing vaccine availability and effectiveness. The data obtained with intradermal delivery of some vaccines are encouraging and warrant further study and development; however significant gaps in knowledge and operational challenges such as reformulation, optimizing vaccine presentation and development of novel devices to aid intradermal vaccine delivery need to be addressed. Modelling of the costs and potential savings resulting from intradermal delivery should be done to provide realistic expectations of the potential benefits and to support cases for investment. Implementation and uptake of intradermal vaccine delivery requires further research and development, which depends upon collaboration between multiple stakeholders in the field of vaccination. PMID:21379418

  8. Intradermal delivery of vaccines: potential benefits and current challenges.

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    Hickling, J K; Jones, K R; Friede, M; Zehrung, D; Chen, D; Kristensen, D

    2011-03-01

    Delivery of vaccine antigens to the dermis and/or epidermis of human skin (i.e. intradermal delivery) might be more efficient than injection into the muscle or subcutaneous tissue, thereby reducing the volumes of antigen. This is known as dose-sparing and has been demonstrated in clinical trials with some, but not all, vaccines. Dose-sparing could be beneficial to immunization programmes by potentially reducing the costs of purchase, distribution and storage of vaccines; increasing vaccine availability and effectiveness. The data obtained with intradermal delivery of some vaccines are encouraging and warrant further study and development; however significant gaps in knowledge and operational challenges such as reformulation, optimizing vaccine presentation and development of novel devices to aid intradermal vaccine delivery need to be addressed. Modelling of the costs and potential savings resulting from intradermal delivery should be done to provide realistic expectations of the potential benefits and to support cases for investment. Implementation and uptake of intradermal vaccine delivery requires further research and development, which depends upon collaboration between multiple stakeholders in the field of vaccination.

  9. Intradermal administration of viral vaccines.

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    Nagafuchi; Kashiwagi; Imayama; Hayashi; Niho

    1998-04-01

    Intradermal administration maybe useful in lowering the cost of vaccination against hepatitis B significantly, and may also be helpful for the rapid induction of antibodies, reversing non-responsiveness, improving postexposure prophylaxis and immunising immunocompromised people. In addition, delayed type hypersensitivity skin reaction to the vaccine could serve as a useful marker for the acquisition of T helper type 1 immunoreactivity in vivo. However, there are some disadvantages when using intradermal vaccinations, including the requirement for skilful administration, the absence of approval from licensing authorities, the development of local skin reactions and a lower antibody response when 1/10 of the standard vaccine dose is used. This requires that appropriate vaccination regimens, including the correct vaccine dosage, and vaccination schedule are followed. In the future, a similar vaccination strategy might also be applied for the prevention and control of other infectious diseases. Copyright 1998 John Wiley & Sons, Ltd.

  10. Lipopolysaccharide contamination in intradermal DNA vaccination : toxic impurity or adjuvant?

    NARCIS (Netherlands)

    Berg, J.H. van den; Quaak, S.G.L.; Beijnen, J.H.; Hennink, W.E.; Storm, G.; Schumacher, T.N.; Haanen, J.B.A.G.; Nuijen, B.

    Purpose: Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal DNA vaccination administered by DNA tattooing. Method: Micewere vaccinated with a model DNA

  11. A new biolistic intradermal injector

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    Brouillette, M.; Doré, M.; Hébert, C.; Spooner, M.-F.; Marchand, S.; Côté, J.; Gobeil, F.; Rivest, M.; Lafrance, M.; Talbot, B. G.; Moutquin, J.-M.

    2016-01-01

    We present a novel intradermal needle-free drug delivery device which exploits the unsteady high-speed flow produced by a miniature shock tube to entrain drug or vaccine particles onto a skin target. A first clinical study of pain and physiological response of human subjects study is presented, comparing the new injector to intramuscular needle injection. This clinical study, performed according to established pain assessment protocols, demonstrated that every single subject felt noticeably less pain with the needle-free injector than with the needle injection. Regarding local tolerance and skin reaction, bleeding was observed on all volunteers after needle injection, but on none of the subjects following powder injection. An assessment of the pharmacodynamics, via blood pressure, of pure captopril powder using the new device on spontaneously hypertensive rats was also performed. It was found that every animal tested with the needle-free injector exhibited the expected pharmacodynamic response following captopril injection. Finally, the new injector was used to study the delivery of an inactivated influenza vaccine in mice. The needle-free device induced serum antibody response to the influenza vaccine that was comparable to that of subcutaneous needle injection, but without requiring the use of an adjuvant. Although no effort was made to optimize the formulation or the injection parameters in the present study, the novel injector demonstrates great promise for the rapid, safe and painless intradermal delivery of systemic drugs and vaccines.

  12. Mycobacterium ulcerans fails to infect through skin abrasions in a guinea pig infection model: implications for transmission.

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    Williamson, Heather R; Mosi, Lydia; Donnell, Robert; Aqqad, Maha; Merritt, Richard W; Small, Pamela L C

    2014-04-01

    Transmission of M. ulcerans, the etiological agent of Buruli ulcer, from the environment to humans remains an enigma despite decades of research. Major transmission hypotheses propose 1) that M. ulcerans is acquired through an insect bite or 2) that bacteria enter an existing wound through exposure to a contaminated environment. In studies reported here, a guinea pig infection model was developed to determine whether Buruli ulcer could be produced through passive inoculation of M. ulcerans onto a superficial abrasion. The choice of an abrasion model was based on the fact that most bacterial pathogens infecting the skin are able to infect an open lesion, and that abrasions are extremely common in children. Our studies show that after a 90d infection period, an ulcer was present at intra-dermal injection sites of all seven animals infected, whereas topical application of M. ulcerans failed to establish an infection. Mycobacterium ulcerans was cultured from all injection sites whereas infected abrasion sites healed and were culture negative. A 14d experiment was conducted to determine how long organisms persisted after inoculation. Mycobacterium ulcerans was isolated from abrasions at one hour and 24 hours post infection, but cultures from later time points were negative. Abrasion sites were qPCR positive up to seven days post infection, but negative at later timepoints. In contrast, M. ulcerans DNA was detected at intra-dermal injection sites throughout the study. M. ulcerans was cultured from injection sites at each time point. These results suggest that injection of M. ulcerans into the skin greatly facilitates infection and lends support for the role of an invertebrate vector or other route of entry such as a puncture wound or deep laceration where bacteria would be contained within the lesion. Infection through passive inoculation into an existing abrasion appears a less likely route of entry.

  13. Varicella infection modeling.

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    Jones, Katherine A.; Finley, Patrick D.; Moore, Thomas W.; Nozick, Linda Karen; Martin, Nathaniel; Bandlow, Alisa; Detry, Richard Joseph; Evans, Leland B.; Berger, Taylor Eugen

    2013-09-01

    Infectious diseases can spread rapidly through healthcare facilities, resulting in widespread illness among vulnerable patients. Computational models of disease spread are useful for evaluating mitigation strategies under different scenarios. This report describes two infectious disease models built for the US Department of Veteran Affairs (VA) motivated by a Varicella outbreak in a VA facility. The first model simulates disease spread within a notional contact network representing staff and patients. Several interventions, along with initial infection counts and intervention delay, were evaluated for effectiveness at preventing disease spread. The second model adds staff categories, location, scheduling, and variable contact rates to improve resolution. This model achieved more accurate infection counts and enabled a more rigorous evaluation of comparative effectiveness of interventions.

  14. comparative study of intradermal smear microscopy

    African Journals Online (AJOL)

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    women with malaria when the converse was the case. The reliability of the test, the positive predictive value, was 77.4%. This is a measure of the probability of intradermal smear to detect malaria parasitaemia in the presence of malaria parasites. That is, it will correctly detect malaria parasitaemia in greater than seven (7) ...

  15. Murine model of rotavirus infection.

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    Feng, N; Franco, M A; Greenberg, H B

    1997-01-01

    The murine model of homologous rotavirus infection has been used to study the determinants of protection. The local IgA immune response appears to be the critical factor in generating protective immunity after natural infection. A series of knockout mice were used to evaluate the contribution of T cells and B cells to immunity and resolution from primary infection. Both arms of immune system played a role in the resolution of primary infection but antibody was much more important for prevention of reinfection.

  16. Variable BCG efficacy in rhesus populations: Pulmonary BCG provides protection where standard intra-dermal vaccination fails.

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    Verreck, Frank A W; Tchilian, Elma Z; Vervenne, Richard A W; Sombroek, Claudia C; Kondova, Ivanela; Eissen, Okke A; Sommandas, Vinod; van der Werff, Nicole M; Verschoor, Ernst; Braskamp, Gerco; Bakker, Jaco; Langermans, Jan A M; Heidt, Peter J; Ottenhoff, Tom H M; van Kralingen, Klaas W; Thomas, Alan W; Beverley, Peter C L; Kocken, Clemens H M

    2017-05-01

    M.bovis BCG vaccination against tuberculosis (TB) notoriously displays variable protective efficacy in different human populations. In non-human primate studies using rhesus macaques, despite efforts to standardise the model, we have also observed variable efficacy of BCG upon subsequent experimental M. tuberculosis challenge. In the present head-to-head study, we establish that the protective efficacy of standard parenteral BCG immunisation varies among different rhesus cohorts. This provides different dynamic ranges for evaluation of investigational vaccines, opportunities for identifying possible correlates of protective immunity and for determining why parenteral BCG immunisation sometimes fails. We also show that pulmonary mucosal BCG vaccination confers reduced local pathology and improves haematological and immunological parameters post-infection in animals that are not responsive to induction of protection by standard intra-dermal BCG. These results have important implications for pulmonary TB vaccination strategies in the future. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Intradermal vaccination for infants and children.

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    Saitoh, Akihiko; Aizawa, Yuta

    2016-09-01

    Intradermal (ID) vaccination induces a more potent immune response and requires lower vaccine doses as compared with standard vaccination routes. To deliver ID vaccines effectively and consistently, an ID delivery device has been developed and is commercially available for adults. The clinical application of ID vaccines for infants and children is much anticipated because children receive several vaccines, on multiple occasions, during infancy and childhood. However, experience with ID vaccines is limited and present evidence is sparse and inconsistent. ID delivery devices are not currently available for infants and children, but recent studies have examined skin thickness in this population and reported that it did not differ in proportion to body size in infants, children, and adults. These results are helpful in developing new ID devices and for preparing new vaccines in infants and children.

  18. Optimizing adjuvants for intradermal delivery of MenC glycoconjugate vaccine.

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    Donadei, Agnese; Balocchi, Cristiana; Romano, Maria R; Panza, Luigi; Adamo, Roberto; Berti, Francesco; O'Hagan, Derek T; Gallorini, Simona; Baudner, Barbara C

    2017-07-13

    Intradermal vaccine delivery is a promising alternative to the conventional intramuscular route. The skin layer is immunologically supported by a densely network of antigen presenting cells, while the skeletal muscle is loaded with a relatively sparse population of APCs. Nevertheless, the vaccine to be suitable for intradermal delivery needs a new formulation to facilitate either smaller injection volumes or the introduction into new delivery devises as micro-needles. This study presents a proof of concept for intradermal delivery of the MenC-CRM 197 glycoconjugate vaccine using a mouse model. Tangential flow filtration allowed obtaining a 20-fold concentrated vaccine formulation suitable for intradermal injection. Importantly the intradermal delivery of non-adjuvanted MenC glycoconjugate vaccine showed a quicker on-set and superiority in terms of immunogenicity compared to intramuscular administration of the respective vaccine and comparable immunogenicity to the aluminum adjuvanted vaccine formulation given intramuscular. Subsequently, the use of adjuvants allowed to further increase the immunogenicity and to modulate the quality of the immune response towards a more beneficial Th1 response. As adjuvants two Toll like receptor agonists (TLR4a and TLR7a), a mutant of the heat-labile enterotoxin from Escherichia coli (LT), a α-GalactosylCeramide analogue and an oil in water emulsion were investigated in order to target skin-resident antigen-presenting cells. This approach has the potential to be extended to other meningococcal serogroups, representing a promising strategy for the development of dermally administered multivalent glycoconjugate vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Anafylaktisk shock efter intradermal injektion af steroidpræparat

    DEFF Research Database (Denmark)

    Meyer, Martin Willy; Zachariae, Claus Otto Carl; Garvey, Lene Heise

    2015-01-01

    Anaphylactic shock after intradermal injection of corticosteroid Carboxymethylcellulose (CMC) is a derivative of cellulose found in many food products, pharmaceuticals and cosmetics. Allergy to carboxymethylcellulose in parenteral corticosteroid preparations leading to anaphylaxis is rare, but has...

  20. Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis.

    Directory of Open Access Journals (Sweden)

    Dominique N Price

    2016-05-01

    Full Text Available Bacille Calmette-Guérin (BCG is currently the only approved vaccine against tuberculosis (TB and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0-80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy. In an effort to elucidate the mechanisms underlying EM interference with BCG vaccine efficacy, we exposed mice chronically to Mycobacterium avium (M. avium, a specific EM, by two different routes, the oral and intradermal route, to mimic human exposure. After intradermal BCG immunization in mice exposed to oral M. avium, we saw a significant decrease in the pro-inflammatory cytokine IFN-γ, and an increase in T regulatory cells and the immunosuppressive cytokine IL-10 compared to naïve BCG-vaccinated animals. To circumvent the immunosuppressive effect of oral M. avium exposure, we vaccinated mice by the pulmonary route with BCG. Inhaled BCG immunization rescued IFN-γ levels and increased CD4 and CD8 T cell recruitment into airways in M. avium-presensitized mice. In contrast, intradermal BCG vaccination was ineffective at T cell recruitment into the airway. Pulmonary BCG vaccination proved protective against Mtb infection regardless of previous oral M. avium exposure, compared to intradermal BCG immunization. In conclusion, our data indicate that vaccination against TB by the pulmonary route increases BCG vaccine efficacy by avoiding the immunosuppressive interference generated by chronic oral exposure to EM. This has implications in TB-burdened countries where drug resistance is on the rise and health care options are limited due to economic considerations. A successful vaccine against TB is necessary in these areas as it is both effective and economical.

  1. Experimental infection of dogs with Leishmania and saliva as a model to study Canine Visceral Leishmaniasis.

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    Dirceu Joaquim Costa

    Full Text Available BACKGROUND: Canine Visceral Leishmaniasis (CVL is a zoonotic disease caused by Leishmania infantum, transmitted by the bite of Lutzomyia longipalpis sand flies. Dogs are the main domestic reservoir of the parasite. The establishment of an experimental model that partially reproduces natural infection in dogs is very important to test vaccine candidates, mainly regarding those that use salivary proteins from the vector and new therapeutical approaches. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we describe an experimental infection in dogs, using intradermal injection of Leishmania infantum plus salivary gland homogenate (SGH of Lutzomyia longipalpis. Thirty-five dogs were infected with 1×10(7 parasites combined with five pairs of Lutzomyia longipalpis salivary glands and followed for 450 days after infection and clinical, immunological and parasitological parameters were evaluated. Two hundred and ten days after infection we observed that 31,4% of dogs did not display detectable levels of anti-Leishmania antibodies but all presented different numbers of parasites in the lymph nodes. Animals with a positive xenodiagnosis had at least 3,35×10(5 parasites in their lymph nodes. An increase of IFN-γ and IL-10 levels was detected during infection. Twenty two percent of dogs developed symptoms of CVL during infection. CONCLUSION: The infection model described here shows some degree of similarity when compared with naturally infected dogs opening new perspectives for the study of CVL using an experimental model that employs the combination of parasites and sand fly saliva both present during natural transmission.

  2. Novel Treatment of Neck Wrinkles with an Intradermal Radiofrequency Device

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    Hyun, Moo Yeol; Li, Kapsok; Kim, Myeung Nam; Hong, Chang Kwun; Kim, Hyuk; Koh, Hyun-Ju; Park, Won-Seok

    2015-01-01

    Neck wrinkles commonly develop owing to the aging process. However, recently, the number of patients with neck wrinkles has been increasing. Also, an increasing number of young patients have presented with this condition, possibly because of the effect of the head-down posture that they adopt when using their computer or smartphone. We report two cases of young adults with a prominent neck wrinkle. In case 1, a 29-year-old woman with a neck wrinkle was treated with six intradermal radiofrequency (RF) procedures. Her neck wrinkle was significantly improved with the RF treatment. In case 2, a 32-year-old woman with a wrinkle and generalized light brownish tiny papules on the neck was treated with three intradermal RF procedures simultaneously with 30% glycolic acid peeling. Her wrinkle and skin tone were improved dramatically. We conclude that intradermal RF has a considerable efficacy for reducing neck wrinkles. PMID:25673937

  3. A Mouse Model of Latent Tuberculosis Infection to Study Intervention Strategies to Prevent Reactivation.

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    Andreas Kupz

    Full Text Available Infection with Mycobacterium tuberculosis (Mtb is the leading cause of death in human immunodeficiency virus (HIV+ individuals, particularly in Sub-Saharan Africa. Management of this deadly co-infection is a significant global health challenge that is exacerbated by the lack of efficient vaccines against both Mtb and HIV, as well as the lack of reliable and robust animal models for Mtb/HIV co-infection. Here we describe a tractable and reproducible mouse model to study the reactivation dynamics of latent Mtb infection following the loss of CD4+ T cells as it occurs in HIV-co-infected individuals. Whereas intradermally (i.d. infected C57BL/6 mice contained Mtb within the local draining lymph nodes, depletion of CD4+ cells led to progressive systemic spread of the bacteria and induction of lung pathology. To interrogate whether reactivation of Mtb after CD4+ T cell depletion can be reversed, we employed interleukin (IL-2/anti-IL-2 complex-mediated cell boost approaches. Although populations of non-CD4 lymphocytes, such as CD8+ memory T cells, natural killer (NK cells and double-negative (DN T cells significantly expanded after IL-2/anti-IL-2 complex treatment, progressive development of bacteremia and pathologic lung alterations could not be prevented. These data suggest that the failure to reverse Mtb reactivation is likely not due to anergy of the expanded cell subsets and rather indicates a limited potential for IL-2-complex-based therapies in the management of Mtb/HIV co-infection.

  4. A Mouse Model of Latent Tuberculosis Infection to Study Intervention Strategies to Prevent Reactivation.

    Science.gov (United States)

    Kupz, Andreas; Zedler, Ulrike; Stäber, Manuela; Kaufmann, Stefan H E

    2016-01-01

    Infection with Mycobacterium tuberculosis (Mtb) is the leading cause of death in human immunodeficiency virus (HIV)+ individuals, particularly in Sub-Saharan Africa. Management of this deadly co-infection is a significant global health challenge that is exacerbated by the lack of efficient vaccines against both Mtb and HIV, as well as the lack of reliable and robust animal models for Mtb/HIV co-infection. Here we describe a tractable and reproducible mouse model to study the reactivation dynamics of latent Mtb infection following the loss of CD4+ T cells as it occurs in HIV-co-infected individuals. Whereas intradermally (i.d.) infected C57BL/6 mice contained Mtb within the local draining lymph nodes, depletion of CD4+ cells led to progressive systemic spread of the bacteria and induction of lung pathology. To interrogate whether reactivation of Mtb after CD4+ T cell depletion can be reversed, we employed interleukin (IL)-2/anti-IL-2 complex-mediated cell boost approaches. Although populations of non-CD4 lymphocytes, such as CD8+ memory T cells, natural killer (NK) cells and double-negative (DN) T cells significantly expanded after IL-2/anti-IL-2 complex treatment, progressive development of bacteremia and pathologic lung alterations could not be prevented. These data suggest that the failure to reverse Mtb reactivation is likely not due to anergy of the expanded cell subsets and rather indicates a limited potential for IL-2-complex-based therapies in the management of Mtb/HIV co-infection.

  5. Anafylaktisk shock efter intradermal injektion af steroidpræparat

    DEFF Research Database (Denmark)

    Meyer, Martin Willy; Zachariae, Claus Otto Carl; Garvey, Lene Heise

    2015-01-01

    Anaphylactic shock after intradermal injection of corticosteroid Carboxymethylcellulose (CMC) is a derivative of cellulose found in many food products, pharmaceuticals and cosmetics. Allergy to carboxymethylcellulose in parenteral corticosteroid preparations leading to anaphylaxis is rare, but has...... previously been reported. We report a case of a 52-year-old woman with prurigo nodularis of Hyde, who reacted with anaphylaxis after intradermal injection of Kenalog 40 mg/ml. Allergy testing showed a positive skin prick test for CMC and the patient was advised to avoid future parenteral exposure to CMC...

  6. Evaluation of the Mycobacterium tuberculosis SO2 vaccine using a natural tuberculosis infection model in goats.

    Science.gov (United States)

    Bezos, J; Casal, C; Álvarez, J; Roy, A; Romero, B; Rodríguez-Bertos, A; Bárcena, C; Díez, A; Juste, R; Gortázar, C; Puentes, E; Aguiló, N; Martín, C; de Juan, L; Domínguez, L

    2017-05-01

    The development of new vaccines against animal tuberculosis (TB) is a priority for improving the control and eradication of this disease, particularly in those species not subjected to compulsory eradication programmes. In this study, the protection conferred by the Mycobacterium tuberculosis SO 2 experimental vaccine was evaluated using a natural infection model in goats. Twenty-six goats were distributed in three groups: (1) 10 goats served as a control group; (2) six goats were subcutaneously vaccinated with BCG; and (3) 10 goats were subcutaneously vaccinated with SO 2 . Four months after vaccination, all groups were merged with goats infected with Mycobacterium bovis or Mycobacterium caprae, and tested over a 40 week period using a tuberculin intradermal test and an interferon-γ assay for mycobacterial reactivity. The severity of lesions was determined at post-mortem examination and the bacterial load in tissues were evaluated by culture. The two vaccinated groups had significantly lower lesion and bacterial culture scores than the control group (P<0.05); at the end of the study, the SO 2 vaccinated goats had the lowest lesion and culture scores. These results suggest that the SO 2 vaccine provides some protection against TB infection acquired from natural exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Susceptible-infected-recovered and susceptible-exposed-infected models

    Energy Technology Data Exchange (ETDEWEB)

    Tome, Tania; De Oliveira, Mario J, E-mail: oliveira@if.usp.br [Instituto de Fisica, Universidade de Sao Paulo, Caixa Postal 66318, 05315-970 Sao Paulo, Sao Paulo (Brazil)

    2011-03-04

    Two stochastic epidemic lattice models, the susceptible-infected-recovered and the susceptible-exposed-infected models, are studied on a Cayley tree of coordination number k. The spreading of the disease in the former is found to occur when the infection probability b is larger than b{sub c} = k/2(k - 1). In the latter, which is equivalent to a dynamic site percolation model, the spreading occurs when the infection probability p is greater than p{sub c} = 1/(k - 1). We set up and solve the time evolution equations for both models and determine the final and time-dependent properties, including the epidemic curve. We show that the two models are closely related by revealing that their relevant properties are exactly mapped into each other when p = b/[k - (k - 1)b]. These include the cluster size distribution and the density of individuals of each type, quantities that have been determined in closed forms.

  8. Intradermal vaccination against hepatitis B in a group of medical ...

    African Journals Online (AJOL)

    A prospective study of a low-dose (one-tenth) intradermal regimen using recombinant hepatitis B vaccine was undertaken during two consecutive years in 4th-year medical students. Eighty one per cent of the vaccinees (123/152) seroconverted with anti-HBs levels of > 10 lU/l. The lower titre of hepatitis B surface antibodies ...

  9. Field study on the safety and efficacy of intradermal versus intramuscular vaccination against Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Beffort, Lisa; Weiß, Christine; Fiebig, Kerstin; Jolie, Rika; Ritzmann, Mathias; Eddicks, Matthias

    2017-09-30

    The present study compares the safety and efficacy of a needle-free, intradermal Mycoplasma hyopneumoniae vaccine to an intramuscular one. 420 piglets (21+3 days of age) were randomly assigned to two vaccination groups (intradermal vaccination V1 (n=138), intramuscular vaccination V2 (n=144)) and one unvaccinated control group (CG, n=138). As safety parameters clinical observations, local injection site reactions (ISR) and rectal temperatures were assessed. Average daily weight gain (ADWG) and pneumonic lung lesions (LL) were measured as efficacy parameters. ISRs were minor in V1. After both vaccinations, no adverse impact on appetite was observed and mean rectal temperatures remained within physiological range. ADWG during the fattening period was significantly higher in vaccinated groups (V1: 913.4 g, V2: 924.5 g) compared with CG (875.6 g). No differences in ADWG were observed between V1 and V2. Vaccinated pigs had a significantly reduced mean extent of LL compared with CG. V1 was superior in reducing the extent and prevalence of LL compared with V2. These results reveal that a needle-free intradermal vaccination is safe and efficacious in reducing both the prevalence and extent of lung lesions, as well as in improving performance parameters, in a farrow-to-finish farm with a late onset of M hyopneumonia e infection. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Cost-effectiveness of an influenza vaccination program offering intramuscular and intradermal vaccines versus intramuscular vaccine alone for elderly.

    Science.gov (United States)

    Leung, Man-Kit; You, Joyce H S

    2016-05-11

    Intradermal (ID) injection is an alternative route for influenza vaccine administration in elderly with potential improvement of vaccine coverage. This study aimed to investigate the cost-effectiveness of an influenza vaccination program offering ID vaccine to elderly who had declined intramuscular (IM) vaccine from the perspective of Hong Kong public healthcare provider. A decision analytic model was used to simulate outcomes of two programs: IM vaccine alone (IM program), and IM or ID vaccine (IM/ID program) in a hypothetic cohort of elderly aged 65 years. Outcome measures included influenza-related direct medical cost, infection rate, mortality rate, quality-adjusted life years (QALYs) loss, and incremental cost per QALY saved (ICER). Model inputs were derived from literature. Sensitivity analyses evaluated the impact of uncertainty of model variables. In base-case analysis, the IM/ID program was more costly (USD52.82 versus USD47.59 per individual to whom vaccine was offered) with lower influenza infection rate (8.71% versus 9.65%), mortality rate (0.021% versus 0.024%) and QALYs loss (0.00336 versus 0.00372) than the IM program. ICER of IM/ID program was USD14,528 per QALY saved. One-way sensitivity analysis found ICER of IM/ID program to exceed willingness-to-pay threshold (USD39,933) when probability of influenza infection in unvaccinated elderly decreased from 10.6% to 5.4%. In 10,000 Monte Carlo simulations of elderly populations of Hong Kong, the IM/ID program was the preferred option in 94.7% of time. An influenza vaccination program offering ID vaccine to elderly who had declined IM vaccine appears to be a highly cost-effective option. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Evaluation of specific humoral immune response in pigs vaccinated intradermally with deleted Aujeszky's disease vaccine and challenged with virulent strain of Herpesvirus suis type 1.

    Science.gov (United States)

    Mikulska-Skupień, E; Szweda, W; Procajło, Z

    2005-01-01

    A comparison of intradermal (ID) versus intramuscular (IM) routes of pig vaccination with deleted Aujeszky's disease (AD) vaccine on the formation of specific postvaccinal and postchallenge humoral immune response was performed. The studies were carried out on 21 eight week-old piglets, divided into three groups--two experimental and one control of 7 piglets each. Animals of first two groups were vaccinated twice in 12 and 16 week of age with deleted, live attenuated AD vaccine Porcilis Begonia (Intervet). Group I was vaccinated with a dose of 2.0 ml (10(6.0) TCID50)) intramuscularly (IM) into neck muscles, and group II received 0.2 ml (10(5.0) TCID50) intradermally (ID) in neck area using needleless apparatus SERENA model SD 1-2 (Emplast, Italy). In group K (control) 2.0 ml PBS IM was used. Seventy days after the first vaccination all pigs were intranasally infected with a dose of 10(5.5) TCID50 of virulent Northern Ireland Aujeszky-3 (NIA-3) strain of Herpesvirus suis type 1 (SHV-1) by instilling 0.5 ml of virus suspension into each nostril. Specific humoral immune response was evaluated using seroneutralization (SN) test and gE-ELISA-Pseudorabies virus gpI Antibody Test Kit (Herd Chek Anti-PRV gpI), IDEXX Lab Inc (USA). It was found that challenge caused anamnestic reaction in both groups of vaccinated pigs, but postchallenge immune response was stronger in ID-vaccinated group--on 14 day post infection (dpi) SN antibody level was considerably higher than in IM-vaccinated group. The obtained results suggest that secondary immunological response after challenge is decidedly more effective in the range of evaluated parameters in animals vaccinated by ID route, which can be linked to, perhaps underestimated yet and seldom utilized, skin immunity mechanisms in specific prophylaxis of infectious diseases. Advantages and disadvantages of SN test and ELISA are also discussed.

  12. Ebola Virus Infection Modelling and Identifiability Problems

    Directory of Open Access Journals (Sweden)

    Van-Kinh eNguyen

    2015-04-01

    Full Text Available The recent outbreaks of Ebola virus (EBOV infections have underlined the impact of the virus as a major threat for human health. Due to the high biosafety classification of EBOV (level 4, basic research is very limited. Therefore, the development of new avenues of thinking to advance quantitative comprehension of the virus and its interaction with the host cells is urgently neededto tackle this lethal disease. Mathematical modelling of the EBOV dynamics can be instrumental to interpret Ebola infection kinetics on quantitative grounds. To the best of our knowledge, a mathematical modelling approach to unravel the interaction between EBOV and the host cells isstill missing. In this paper, a mathematical model based on differential equations is used to represent the basic interactions between EBOV and wild-type Vero cells in vitro. Parameter sets that represent infectivity of pathogens are estimated for EBOV infection and compared with influenza virus infection kinetics. The average infecting time of wild-type Vero cells in EBOV is slower than in influenza infection. Simulation results suggest that the slow infecting time of EBOV could be compensated by its efficient replication. This study reveals several identifiability problems and what kind of experiments are necessary to advance the quantification of EBOV infection. A first mathematical approach of EBOV dynamics and the estimation of standard parametersin viral infections kinetics is the key contribution of this work, paving the way for future modelling work on EBOV infection.

  13. Efficacy of bicarbonate in decreasing pain on intradermal injection of local anesthetics: a meta-analysis.

    Science.gov (United States)

    Hanna, Marie N; Elhassan, Amir; Veloso, Patricia M; Lesley, Maggie; Lissauer, Jon; Richman, Jeffrey M; Wu, Christopher L

    2009-01-01

    Intradermal injection of local anesthetic often results in pain on injection due in part to the acidic pH of commercially prepared solutions, which are optimized to prolong shelf life. Although there are other possible explanations (eg, noxious properties of local anesthetics, pressure effect of infiltration), the etiology is most likely multifactorial. Although addition of bicarbonate to local anesthetics may decrease pain on intradermal injection, the extent of this analgesic effect is uncertain. We performed a meta-analysis of available trials investigating pain during intradermal injection of buffered local anesthetic preparations. We searched the National Library of Medicine's PubMed database for all relevant articles published on the topic through November 2006. Inclusion criteria included double-blind, randomized controlled trials and use of a visual analog scale to measure pain on infiltration of local anesthetic buffered with sodium bicarbonate compared with that of unbuffered local anesthetic. Meta-analysis was performed using the Review Manager 4.2.7 (The Cochrane Collaboration, 2004). A random-effects model was used. Our search resulted in 86 abstracts, of which 12 articles met all inclusion criteria. Overall, there were 609 observations for buffered local anesthetic and 615 for unbuffered local anesthetic. Use of buffered local anesthetic resulted in a statistically lower weighted mean difference in visual analog scale of -1.17 (95% confidence interval, -1.68 to -0.67) compared with unbuffered local anesthetic. Our systematic review suggests that the use of buffered local anesthetics seems to be associated with a statistical decrease in pain of infiltration when compared with unbuffered local anesthetic.

  14. Intradermal Melanocytic Nevus Containing Bone Metaplasia: A Case Report

    Directory of Open Access Journals (Sweden)

    Recep Bedir

    2013-06-01

    Full Text Available Melanocytic nevi in the bone metaplasia is not a common case. The majority of these lesions tend to be located in the upper part of the body, as in our case. There is a higher incidence of females. In the pathogenesis usually is thought to develop seconder damage of the hair follicles. We report a 46-year-old woman who presented a case of osseous metaplasia within a benign intradermal melanocytic nevus was excised from the face.

  15. Intradermal vaccination against hepatitis B in a group of medical ...

    African Journals Online (AJOL)

    A prospective study of a low-dose (one-tenth) intradermal regimen using recombinant hepatitis B vaccine was under- taken during two consecutive years in 4th-year medical stu- dents. Eightj;one per cent of the vaccinees (123/152) sero- converted with anti.HBs levels of> 10 lUll. The lower titre of hepatitis B surface ...

  16. Evaluation of intravenous fluorescein in intradermal allergy testing in psittacines.

    Science.gov (United States)

    Nett, Claudia S; Hosgood, Giselle; Heatley, J Jill; Foil, Carol S; Tully, Thomas N

    2003-12-01

    This study was designed to improve the clinical feasibility of intradermal skin testing of psittacine birds using intravenous fluorescein stain. Twenty-five healthy, anaesthetized Hispaniolan Amazon parrots (Amazona ventralis) were injected intravenously with 10 mg kg-1 fluorescein-sodium 1% followed by intradermal injections of 0.02 mL phosphate-buffered saline, histamine phosphate (1:100,000 w/v) and codeine phosphate (1:100,000 w/v) at the sternal apteria. Wheal diameters of reaction sites were measured grossly and under illumination with a Wood's lamp after 5 and 10 min. Fluorescence-enhanced injection sites were scored between 0 and 2, with 0 equivalent to normal skin and 2 equivalent to a plucked feather follicle. The presence of a fluorescent halo around intradermal injections was also recorded. Under Wood's light illumination at 10 min, histamine and saline were evaluated as positive and negative controls, respectively, based on a positive test having a halo and a score of 2. Sensitivity and specificity were each 76% for halo, 84 and 42% for score and 64 and 77% for combination of score and halo, respectively. Further, mean histamine reactions were significantly larger than codeine phosphate and saline (8.8 +/- 0.4 mm; 7.2 +/- 0.3 mm; 5.9 +/- 0.6 mm); however, this finding was not consistent in individual birds. Wheal size, halo presence and score were affected by site location independent from the injected compound. Intravenous fluorescein improved the readability of avian skin tests; however, the compounds tested raised inconsistent reactions in wheal size, score or halo presence. The compound-independent site effect raises concern on the validity of avian skin testing and warrants investigation of other techniques such as in vitro allergy testing. Based on our findings, intradermal allergy testing in psittacines with or without fluorescein is unreliable and cannot be recommended for practical clinical use.

  17. Changes in human Langerhans cells following intradermal injection of influenza virus-like particle vaccines.

    Directory of Open Access Journals (Sweden)

    Marc Pearton

    Full Text Available There is a significant gap in our fundamental understanding of early morphological and migratory changes in human Langerhans cells (LCs in response to vaccine stimulation. As the vast majority of LCs studies are conducted in small animal models, substantial interspecies variation in skin architecture and immunity must be considered when extrapolating the results to humans. This study aims to determine whether excised human skin, maintained viable in organ culture, provides a useful human model for measuring and understanding early immune response to intradermally delivered vaccine candidates. Excised human breast skin was maintained viable in air-liquid-interface organ culture. This model was used for the first time to show morphological changes in human LCs stimulated with influenza virus-like particle (VLP vaccines delivered via intradermal injection. Immunohistochemistry of epidermal sheets and skin sections showed that LCs in VLP treated skin lost their typical dendritic morphology. The cells were more dispersed throughout the epidermis, often in close proximity to the basement membrane, and appeared vertically elongated. Our data provides for increased understanding of the complex morphological, spatial and temporal changes that occur to permit LC migration through the densely packed keratinocytes of the epidermis following exposure to vaccine. Significantly, the data not only supports previous animal data but also provides new and essential evidence of host response to this vaccination strategy in the real human skin environment.

  18. Mouse Model of Burn Wound and Infection

    DEFF Research Database (Denmark)

    Calum, Henrik; Høiby, Niels; Moser, Claus

    2017-01-01

    The immunosuppression induced by thermal injury renders the burned victim susceptible to infection. A mouse model was developed to examine the immunosuppression, which was possible to induce even at a minor thermal insult of 6% total body surface area. After induction of the burn (48 hr......) a depression of leukocytes in the peripheral blood was found of the burned mice. This depression was due to a reduction in the polymorphonuclear cells. The burned mice were not able to clear a Pseudomonas aeruginosa wound infection, since the infection spread to the blood as compared to mice only infected...... with P. aeruginosa subcutaneously. The burn model offers an opportunity to study infections under these conditions. The present model can also be used to examine new antibiotics and immune therapy. Our animal model resembling the clinical situation is useful in developing new treatments of burn wound...

  19. False-negative reactions to the comparative intradermal tuberculin test for bovine tuberculosis

    Directory of Open Access Journals (Sweden)

    Rudielle A. Rodrigues

    Full Text Available ABSTRACT: According to the Brazilian National Program for the Control and Eradication of Animal Brucellosis and Tuberculosis (PNCEBT, the routine tests for the diagnosis of bovine tuberculosis in the country are the simple intradermal tuberculin test (SITT of the Ministry of Agriculture, Livestock and Food Supply (MAPA, the caudal fold test and the comparative intradermal tuberculin test (CITT. The latter is also used as a confirmatory test. A group of 53 animals from three dairy herds in a focal area for bovine tuberculosis, that were submitted to depopulation in the state of Rio Grande do Sul, were submitted to the CITT. Tissues were cultured and the resulting colonies were confirmed by PCR and DNA sequencing. Among the 53 animals analyzed using the CITT, 32 (60.4% were negative, 14 (26.4% were positive and seven (13.2% results were inconclusive. The CITT detected 11 of the 39 animals with culture-confirmed M. bovis infection as positive. Among the total of 14 uninfected animals based on cultures, the CBT detected eight as negative. Thus, the CITT demonstrated sensitivity of 28.2% and specificity of 57.1% for the population sampled. A total of 24/32 (75.0% of the animals with negative CITT results were culture positive (confirmed by PCR and were considered false negatives based on the CITT. The maintenance of these false-negative animals in herds has serious implications for the control of the disease, since they can be a source of infection. The addition of complementary tests could help identify such animals and increase the odds of diagnostic success.

  20. Mesoporous Silica Nanoparticle-Coated Microneedle Arrays for Intradermal Antigen Delivery.

    Science.gov (United States)

    Tu, Jing; Du, Guangsheng; Reza Nejadnik, M; Mönkäre, Juha; van der Maaden, Koen; Bomans, Paul H H; Sommerdijk, Nico A J M; Slütter, Bram; Jiskoot, Wim; Bouwstra, Joke A; Kros, Alexander

    2017-08-01

    To develop a new intradermal antigen delivery system by coating microneedle arrays with lipid bilayer-coated, antigen-loaded mesoporous silica nanoparticles (LB-MSN-OVA). Synthesis of MSNs with 10-nm pores was performed and the nanoparticles were loaded with the model antigen ovalbumin (OVA), and coated with a lipid bilayer (LB-MSN-OVA). The uptake of LB-MSN-OVA by bone marrow-derived dendritic cells (BDMCs) was studied by flow cytometry. The designed LB-MSN-OVA were coated onto pH-sensitive pyridine-modified microneedle arrays and the delivery of LB-MSN-OVA into ex vivo human skin was studied. The synthesized MSNs demonstrated efficient loading of OVA with a maximum loading capacity of about 34% and the lipid bilayer enhanced the colloidal stability of the MSNs. Uptake of OVA loaded in LB-MSN-OVA by BMDCs was higher than that of free OVA, suggesting effective targeting of LB-MSN-OVA to antigen-presenting cells. Microneedles were readily coated with LB-MSN-OVA at pH 5.8, yielding 1.5 μg of encapsulated OVA per microneedle array. Finally, as a result of the pyridine modification, LB-MSN-OVA were effectively released from the microneedles upon piercing the skin. Microneedle arrays coated with LB-MSN-OVA were successfully developed and shown to be suitable for intradermal delivery of the encapsulated protein antigen.

  1. Use of intradermal botulinum toxin to reduce sebum production and facial pore size.

    Science.gov (United States)

    Shah, Anil R

    2008-09-01

    Review the safety profile and subjective efficacy of intradermal botulinum toxin type A in facial pore size and sebum production. Retrospective analysis of 20 patients. Twenty consecutive patients with a single application of intradermal botulinum toxin type A were examined: Patients (17/20) noted an improvement in sebum production and a decrease in pores size at 1 month after injection. No complications were observed, and 17/20 patients were satisfied with the procedure. Preliminary data suggests that intradermal botulinum toxin may play a role in decreasing sebum production. Further quantitive study may be necessary to determine effects of intradermal botulinum toxin on pore size.

  2. Pair formation models for sexually transmitted infections : A primer

    NARCIS (Netherlands)

    Kretzschmar, MEE; Heijne, Janneke C M

    For modelling sexually transmitted infections, duration of partnerships can strongly influence the transmission dynamics of the infection. If partnerships are monogamous, pairs of susceptible individuals are protected from becoming infected, while pairs of infected individuals delay onward

  3. Anafylaktisk shock efter intradermal injektion af steroidpræparat

    DEFF Research Database (Denmark)

    Meyer, Martin Willy; Zachariae, Claus; Garvey, Lene Heise

    2015-01-01

    Carboxymethylcellulose (CMC) is a derivative of cellulose found in many food products, pharmaceuticals and cosmetics. Allergy to CMC in parenteral corticosteroid preparations leading to anaphylaxis is rare, but has previously been reported. We report a case of a 52-year-old woman with prurigo...... nodularis of Hyde, who reacted with anaphylaxis after intradermal injection of Kenalog 40 mg/ml. Allergy testing showed a positive skin prick test for CMC and the patient was advised to avoid future parenteral exposure to CMC. This case highlights the need to examine excipients in severe cases of drug...

  4. Panton-Valentine leukocidin does play a role in the early stage of Staphylococcus aureus skin infections: a rabbit model.

    Directory of Open Access Journals (Sweden)

    Urszula Lipinska

    Full Text Available Despite epidemiological data linking necrotizing skin infections with the production of Panton-Valentine leukocidin (PVL, the contribution of this toxin to the virulence of S. aureus has been highly discussed as a result of inconclusive results of in vivo studies. However, the majority of these results originate from experiments using mice, an animal species which neutrophils--the major target cells for PVL--are highly insensitive to the action of this leukocidin. In contrast, the rabbit neutrophils have been shown to be as sensitive to PVL action as human cells, making the rabbit a better experimental animal to explore the PVL role. In this study we examined whether PVL contributes to S. aureus pathogenicity by means of a rabbit skin infection model. The rabbits were injected intradermally with 10(8 cfu of either a PVL positive community-associated methicillin-resistant S. aureus isolate, its isogenic PVL knockout or a PVL complemented knockout strain, and the development of skin lesions was observed. While all strains induced skin infection, the wild type strain produced larger lesions and a higher degree of skin necrosis compared to the PVL knockout strain in the first week after the infection. The PVL expression in the rabbits was indirectly confirmed by a raise in the serum titer of anti-LukS-PV antibodies observed only in the rabbits infected with PVL positive strains. These results indicate that the rabbit model is more suitable for studying the role of PVL in staphylococcal diseases than other animal models. Further, they support the epidemiological link between PVL producing S. aureus strains and necrotizing skin infections.

  5. Organoid and Enteroid Modeling of Salmonella Infection

    Directory of Open Access Journals (Sweden)

    Yuebang Yin

    2018-04-01

    Full Text Available Salmonella are Gram-negative rod-shaped facultative anaerobic bacteria that are comprised of over 2,000 serovars. They cause gastroenteritis (salmonellosis with headache, abdominal pain and diarrhea clinical symptoms. Salmonellosis brings a heavy burden for the public health in both developing and developed countries. Antibiotics are usually effective in treating the infected patients with severe gastroenteritis, although antibiotic resistance is on the rise. Understanding the molecular mechanisms of Salmonella infection is vital to combat the disease. In vitro immortalized 2-D cell lines, ex vivo tissues/organs and several animal models have been successfully utilized to study Salmonella infections. Although these infection models have contributed to uncovering the molecular virulence mechanisms, some intrinsic shortcomings have limited their wider applications. Notably, cell lines only contain a single cell type, which cannot reproduce some of the hallmarks of natural infections. While ex vivo tissues/organs alleviate some of these concerns, they are more difficult to maintain, in particular for long term experiments. In addition, non-human animal models are known to reflect only part of the human disease process. Enteroids and induced intestinal organoids are emerging as effective infection models due to their closeness in mimicking the infected tissues/organs. Induced intestinal organoids are derived from iPSCs and contain mesenchymal cells whereas enteroids are derive from intestinal stem cells and are comprised of epithelial cells only. Both enteroids and induced intestinal organoids mimic the villus and crypt domains comparable to the architectures of the in vivo intestine. We review here that enteroids and induced intestinal organoids are emerging as desired infection models to study bacterial-host interactions of Salmonella.

  6. The Hydrodynamics of Needle-Free Intradermal Jet Injection

    Science.gov (United States)

    Simmons, Jonathan; Marston, Jeremy; Fisher, Paul; Broderick, Kate

    2017-11-01

    Needle-free methods of drug delivery circumvent the drawbacks associated with the use of hypodermic needles such as needle-stick injuries, needle-phobia, cross contamination and disposal. Furthermore, pioneering DNA-based vaccines that aim to treat cancer and fight infectious diseases, such as HIV, Ebola and Zika, require precise deposition into the skin to target the immune response producing cells found only in the epidermis and dermis. Intradermal (ID) delivery can be achieved using a needle and the Mantoux technique but this requires a highly skilled technician and so extensive use of DNA vaccines calls for an alternative method of delivery. One option is jet injection which has been employed in mass vaccination programs for intramuscular or subcutaneous delivery and is used by some diabetic patients to inject insulin. In this talk I will present results from our ongoing ex-vivo experimental study into ID jet injection. Ultra-high-speed imaging is used to visualize the process of the jet exiting the nozzle and striking excised skin. A skin bleb grows as liquid is deposited within the skin. I will discuss how the control parameters, such as the rheological profile of the liquid and the stand-off distance, influence the volume of liquid successfully delivered intradermally.

  7. Animal Models of Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Eva Harris

    2012-01-01

    Full Text Available The development of animal models of dengue virus (DENV infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the ‘vascular-leak’ syndrome seen in severe dengue in humans. Humanized mouse models can sustain DENV replication and show some signs of disease, but further development is needed to validate the immune response. Classically, immunocompetent mice infected with DENV do not manifest disease or else develop paralysis when inoculated intracranially; however, a new model using high doses of DENV has recently been shown to develop hemorrhagic signs after infection. Overall, each model has its advantages and disadvantages and is differentially suited for studies of dengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs and vaccines.

  8. Intradermal adipocytes mediate fibroblast recruitment during skin wound healing

    Science.gov (United States)

    Schmidt, Barbara A.; Horsley, Valerie

    2013-01-01

    Acute wound healing in the skin involves the communication of multiple cell types to coordinate keratinocyte and fibroblast proliferation and migration for epidermal and dermal repair. Many studies have focused on the interplay between hematopoietic cells, keratinocytes and fibroblasts during skin wound healing, yet the possible roles for other cell types within the skin, such as intradermal adipocytes, have not been investigated during this process. Here, we identify that adipocyte lineage cells are activated and function during acute skin wound healing. We find that adipocyte precursor cells proliferate and mature adipocytes repopulate skin wounds following inflammation and in parallel with fibroblast migration. Functional analysis of mice with defects in adipogenesis demonstrates that adipocytes are necessary for fibroblast recruitment and dermal reconstruction. These data implicate adipocytes as a key component of the intercellular communication that mediates fibroblast function during skin wound healing. PMID:23482487

  9. Simplification of intradermal skin testing in Hymenoptera venom allergic children.

    Science.gov (United States)

    Cichocka-Jarosz, Ewa; Stobiecki, Marcin; Brzyski, Piotr; Rogatko, Iwona; Nittner-Marszalska, Marita; Sztefko, Krystyna; Czarnobilska, Ewa; Lis, Grzegorz; Nowak-Węgrzyn, Anna

    2017-03-01

    The direct comparison between children and adults with Hymenoptera venom anaphylaxis (HVA) has never been extensively reported. Severe HVA with IgE-documented mechanism is the recommendation for venom immunotherapy, regardless of age. To determine the differences in the basic diagnostic profile between children and adults with severe HVA and its practical implications. We reviewed the medical records of 91 children and 121 adults. Bee venom allergy was exposure dependent, regardless of age (P bee venom allergic group, specific IgE levels were significantly higher in children (29.5 kU A /L; interquartile range, 11.30-66.30 kU A /L) compared with adults (5.10 kU A /L; interquartile range, 2.03-8.30 kU A /L) (P venom were higher in bee venom allergic children compared with the wasp venom allergic children (P venom. At concentrations lower than 0.1 μg/mL, 16% of wasp venom allergic children and 39% of bee venom allergic children had positive intradermal test results. The median tryptase level was significantly higher in adults than in children for the entire study group (P = .002), as well as in bee (P = .002) and wasp venom allergic groups (P = .049). The basic diagnostic profile in severe HVA reactors is age dependent. Lower skin test reactivity to culprit venom in children may have practical application in starting the intradermal test procedure with higher venom concentrations. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. Molecular and Cellular Dynamics in the Skin, the Lymph Nodes, and the Blood of the Immune Response to Intradermal Injection of Modified Vaccinia Ankara Vaccine

    Directory of Open Access Journals (Sweden)

    Pierre Rosenbaum

    2018-04-01

    Full Text Available New vaccine design approaches would be greatly facilitated by a better understanding of the early systemic changes, and those that occur at the site of injection, responsible for the installation of a durable and oriented protective response. We performed a detailed characterization of very early infection and host response events following the intradermal administration of the modified vaccinia virus Ankara as a live attenuated vaccine model in non-human primates. Integrated analysis of the data obtained from in vivo imaging, histology, flow cytometry, multiplex cytokine, and transcriptomic analysis using tools derived from systems biology, such as co-expression networks, showed a strong early local and systemic inflammatory response that peaked at 24 h, which was then progressively replaced by an adaptive response during the installation of the host response to the vaccine. Granulocytes, macrophages, and monocytoid cells were massively recruited during the local innate response in association with local productions of GM-CSF, IL-1β, MIP1α, MIP1β, and TNFα. We also observed a rapid and transient granulocyte recruitment and the release of IL-6 and IL-1RA, followed by a persistent phase involving inflammatory monocytes. This systemic inflammation was confirmed by molecular signatures, such as upregulations of IL-6 and TNF pathways and acute phase response signaling. Such comprehensive approaches improve our understanding of the spatiotemporal orchestration of vaccine-elicited immune response, in a live-attenuated vaccine model, and thus contribute to rational vaccine development.

  11. A clinical decision support system for diagnosis of Allergic Rhinitis based on intradermal skin tests.

    Science.gov (United States)

    Jabez Christopher, J; Khanna Nehemiah, H; Kannan, A

    2015-10-01

    Allergic Rhinitis is a universal common disease, especially in populated cities and urban areas. Diagnosis and treatment of Allergic Rhinitis will improve the quality of life of allergic patients. Though skin tests remain the gold standard test for diagnosis of allergic disorders, clinical experts are required for accurate interpretation of test outcomes. This work presents a clinical decision support system (CDSS) to assist junior clinicians in the diagnosis of Allergic Rhinitis. Intradermal Skin tests were performed on patients who had plausible allergic symptoms. Based on patient׳s history, 40 clinically relevant allergens were tested. 872 patients who had allergic symptoms were considered for this study. The rule based classification approach and the clinical test results were used to develop and validate the CDSS. Clinical relevance of the CDSS was compared with the Score for Allergic Rhinitis (SFAR). Tests were conducted for junior clinicians to assess their diagnostic capability in the absence of an expert. The class based Association rule generation approach provides a concise set of rules that is further validated by clinical experts. The interpretations of the experts are considered as the gold standard. The CDSS diagnoses the presence or absence of rhinitis with an accuracy of 88.31%. The allergy specialist and the junior clinicians prefer the rule based approach for its comprehendible knowledge model. The Clinical Decision Support Systems with rule based classification approach assists junior doctors and clinicians in the diagnosis of Allergic Rhinitis to make reliable decisions based on the reports of intradermal skin tests. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Approximate analytical modeling of leptospirosis infection

    Science.gov (United States)

    Ismail, Nur Atikah; Azmi, Amirah; Yusof, Fauzi Mohamed; Ismail, Ahmad Izani

    2017-11-01

    Leptospirosis is an infectious disease carried by rodents which can cause death in humans. The disease spreads directly through contact with feces, urine or through bites of infected rodents and indirectly via water contaminated with urine and droppings from them. Significant increase in the number of leptospirosis cases in Malaysia caused by the recent severe floods were recorded during heavy rainfall season. Therefore, to understand the dynamics of leptospirosis infection, a mathematical model based on fractional differential equations have been developed and analyzed. In this paper an approximate analytical method, the multi-step Laplace Adomian decomposition method, has been used to conduct numerical simulations so as to gain insight on the spread of leptospirosis infection.

  13. Using Intradermal Rabies Vaccine to Boost Immunity in People with Low Rabies Antibody Levels

    OpenAIRE

    Brown, David; Fooks, Anthony R.; Schweiger, Martin

    2011-01-01

    Intradermal rabies vaccine is recommended by the World Health Organisation, but not all countries, including England, follow this recommendation. A group of 12 adults in England previously given pre-exposure intradermal rabies vaccine were considered to be non-immune to rabies because their rabies antibody titres were known to be less than 0.5 IU/mL. A cohort study examined the immunizing effect of increasing the participants' cumulative dose of intradermal rabies to 2.0 IU. All patients subs...

  14. Intradermal vaccination with un-adjuvanted sub-unit vaccines triggers skin innate immunity and confers protective respiratory immunity in domestic swine.

    Science.gov (United States)

    Le Luduec, Jean-Benoît; Debeer, Sabine; Piras, Fabienne; Andréoni, Christine; Boudet, Florence; Laurent, Philippe; Kaiserlian, Dominique; Dubois, Bertrand

    2016-02-10

    Intradermal (ID) vaccination constitutes a promising approach to induce anti-infectious immunity. This route of immunization has mostly been studied with influenza split-virion vaccines. However, the efficacy of ID vaccination for sub-unit vaccines in relation to underlying skin innate immunity remains to be explored for wider application in humans. Relevant animal models that more closely mimic human skin immunity than the widely used mouse models are therefore necessary. Here, we show in domestic swine, which shares striking anatomic and functional properties with human skin, that a single ID delivery of pseudorabies virus (PRV) glycoproteins without added adjuvant is sufficient to trigger adaptive cellular and humoral immune responses, and to confer protection from a lethal respiratory infection with PRV. Analysis of early events at the skin injection site revealed up-regulation of pro-inflammatory cytokine and chemokine genes, recruitment of neutrophils and monocytes and accumulation of inflammatory DC. We further show that the sustained induction of pro-inflammatory cytokine genes results from the combined effects of skin puncture, liquid injection in the dermis and viral antigens. These data highlight that immune protection against respiratory infection can be induced by ID vaccination with a subunit vaccine and reveal that adjuvant requirements are circumvented by the mechanical and antigenic stress caused by ID injection, which triggers innate immunity and mobilization of inflammatory DC at the immunization site. ID vaccination with sub-unit vaccines may thus represent a safe and efficient solution for protection against respiratory infections in swine and possibly also in humans, given the similarity of skin structure and function in both species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Dengue human infection models supporting drug development.

    Science.gov (United States)

    Whitehorn, James; Van, Vinh Chau Nguyen; Simmons, Cameron P

    2014-06-15

    Dengue is a arboviral infection that represents a major global health burden. There is an unmet need for effective dengue therapeutics to reduce symptoms, duration of illness and incidence of severe complications. Here, we consider the merits of a dengue human infection model (DHIM) for drug development. A DHIM could allow experimentally controlled studies of candidate therapeutics in preselected susceptible volunteers, potentially using smaller sample sizes than trials that recruited patients with dengue in an endemic country. In addition, the DHIM would assist the conduct of intensive pharmacokinetic and basic research investigations and aid in determining optimal drug dosage. Furthermore, a DHIM could help establish proof of concept that chemoprophylaxis against dengue is feasible. The key challenge in developing the DHIM for drug development is to ensure the model reliably replicates the typical clinical and laboratory features of naturally acquired, symptomatic dengue. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  16. Transdermal and intradermal delivery of therapeutic agents: application of physical technologies

    National Research Council Canada - National Science Library

    Banga, Ajay K

    2011-01-01

    .... Advancements in science combined with the need for diverse drug delivery modalities have introduced a variety of transdermal and intradermal products for existing drugs at a fraction of the cost of new drug development...

  17. Self-Assembly DNA Polyplex Vaccine inside Dissolving Microneedles for High-Potency Intradermal Vaccination

    Science.gov (United States)

    Liao, Jing-Fong; Lee, Jin-Ching; Lin, Chun-Kuang; Wei, Kuo-Chen; Chen, Pin-Yuan; Yang, Hung-Wei

    2017-01-01

    The strong immunogenicity induction is the powerful weapon to prevent the virus infections. This study demonstrated that one-step synthesis of DNA polyplex vaccine in microneedle (MN) patches can induce high immunogenicity through intradermal vaccination and increase the vaccine stability for storage outside the cold chain. More negative charged DNA vaccine was entrapped into the needle region of MNs followed by DNA polyplex formation with branched polyethylenimine (bPEI) pre-coated in the cavities of polydimethylsiloxane (PDMS) molds that can deliver more DNA vaccine to immune-cell rich epidermis with high transfection efficiency. Our data in this study support the safety and immunogenicity of the MN-based vaccine; the MN patch delivery system induced an immune response 3.5-fold as strong as seen with conventional intramuscular administration; the DNA polyplex formulation provided excellent vaccine stability at high temperature (could be stored at 45ºC for at least 4 months); the DNA vaccine is expected to be manufactured at low cost and not generate sharps waste. We think this study is significant to public health because there is a pressing need for an effective vaccination in developing countries. PMID:28819449

  18. Efficacy of intradermal mesotherapy in cellulite reduction - Conventional and high-frequency ultrasound monitoring results.

    Science.gov (United States)

    Sylwia, Malinowska; Krzysztof, Mlosek Robert

    2017-10-01

    Cellulite affects the majority of women and is an unacceptable cosmetic defect. Therefore, effective methods for cellulite reduction are being sought. Intradermal mesotherapy is one of such methods. The aim of the study was to assess the efficacy of intradermal mesotherapy in cellulite reduction, using conventional and high-frequency ultrasound. Twenty-one women with cellulite underwent a series of intradermal mesotherapy procedures. The following parameters were assessed: thickness of epidermis, dermis and hypodermis, echogenicity of dermis and the surface area of serrated hypodermis-dermis junction. Furthermore, the thigh circumference was measured; body mass index and cellulite severity were assessed based on photographs using Nürnberger-Müller's scale. Intradermal mesotherapy reduced severity of cellulite. The surface area of serrated hypodermis-dermis junction and hypodermis thickness decreased significantly as compared to baseline. Cellulite reduction was also confirmed by palpation, decreased thigh circumference and the Nürnberger-Müller's grade. There were no statistically significant changes in epidermis or dermis thickness, body weight and the BMI. Intradermal mesotherapy offers effective cellulite reduction. It is a simple and safe treatment, which makes it popular. Further research in mesotherapy is essential due to a limited number of published studies. Ultrasound is a useful method to monitor intradermal mesotherapy and assess its efficacy.

  19. Modeling human influenza infection in the laboratory

    Directory of Open Access Journals (Sweden)

    Radigan KA

    2015-08-01

    Full Text Available Kathryn A Radigan,1 Alexander V Misharin,2 Monica Chi,1 GR Scott Budinger11Division of Pulmonary and Critical Care Medicine, 2Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: Influenza is the leading cause of death from an infectious cause. Because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza A virus replication, the immune response to the virus, and the efficacy of novel therapies. This review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models – mice and ferrets – most frequently used by researchers as models of human influenza infection.Keywords: mice, ferret, influenza, animal model, biosafety

  20. Intradermal Alcian-Blue Injection Method to Trace Acupuncture Meridians

    Directory of Open Access Journals (Sweden)

    Baeckkyoung Sung

    2008-06-01

    Full Text Available Objective : In this article, we report on the intradermal Alcian blue staining method for tracing the meridians of acupuncture. Methods : 1% Alcian blue solution was injected into acupoints by using a 0.5mL insulin syringe with a 31-gauge needle, then the skin was incised and was observed under a stereoscopic microscope. The specimens were examined by using immunohistochemical methods and were observed under a confocal laser scanning microscope. Results : A threadlike structure, which was visualized with Alcian blue, existed in dermis layer and proceeded to hypodermis. In this structure, characteristic alignments of rod- shaped nuclei and 1-2μm sized DNA granules were observed. Furthermore, abundant blood capillary plexuses, peripheral nerve endings, and a corpusclelike structure(about 300μm in diameter were visualized in the skin tissues of acupoints. Conclusion : It was concluded that the specific threadlike and corpuscle-like structures corresponded to superficial Bonghan duct and corpuscle, respectively.

  1. Immune modulating effects of NKT cells in a physiologically low dose Leishmania major infection model after αGalCer analog PBS57 stimulation.

    Directory of Open Access Journals (Sweden)

    Klaus G Griewank

    2014-06-01

    Full Text Available Leishmaniasis is a parasitic infection affecting ∼12 million people worldwide, mostly in developing countries. Treatment options are limited and no effective vaccines exist to date. Natural Killer T (NKT cells are a conserved innate-like lymphocyte population with immunomodulating effects in various settings. A number of reports state a role of NKT cells in different models of Leishmania infection. Here, we investigated the effect of NKT cells in a physiologically relevant, intradermal low dose infection model. After inoculation of 103 infectious-stage L. major, comparable numbers of skin-immigrating NKT cells in both susceptible BALB/c mice and resistant C57BL/6 mice were noted. Compared to their wild type counterparts, NKT cell-deficient mice on a C57BL/6 background were better able to contain infection with L. major and showed decreased IL-4 production in cytokine analysis performed 5 and 8 weeks after infection. Low doses of the NKT cell stimulating αGalCer analog PBS57 applied at the time of infection led to disease exacerbation in C57BL/6 wild-type, but not NKT-deficient mice. The effect was dependent both on the timing and amount of PBS57 administered. The effect of NKT cell stimulation by PBS57 proved to be IL-4 dependent, as it was neutralized in IL-4-deficient C57BL/6 or anti-IL-4 antibody-treated wild-type mice. In contrast to C57BL/6 mice, administration of PBS57 in susceptible BALB/c mice resulted in an improved course of disease. Our results reveal a strain- and cytokine-dependent regulatory role of NKT cells in the development of immunity to low dose L. major infections. These effects, probably masked in previous studies using higher parasite inocula, should be considered in future therapy and immunization approaches.

  2. Immune modulating effects of NKT cells in a physiologically low dose Leishmania major infection model after αGalCer analog PBS57 stimulation.

    Science.gov (United States)

    Griewank, Klaus G; Lorenz, Beate; Fischer, Michael R; Boon, Louis; Lopez Kostka, Susanna; von Stebut, Esther

    2014-06-01

    Leishmaniasis is a parasitic infection affecting ∼12 million people worldwide, mostly in developing countries. Treatment options are limited and no effective vaccines exist to date. Natural Killer T (NKT) cells are a conserved innate-like lymphocyte population with immunomodulating effects in various settings. A number of reports state a role of NKT cells in different models of Leishmania infection. Here, we investigated the effect of NKT cells in a physiologically relevant, intradermal low dose infection model. After inoculation of 103 infectious-stage L. major, comparable numbers of skin-immigrating NKT cells in both susceptible BALB/c mice and resistant C57BL/6 mice were noted. Compared to their wild type counterparts, NKT cell-deficient mice on a C57BL/6 background were better able to contain infection with L. major and showed decreased IL-4 production in cytokine analysis performed 5 and 8 weeks after infection. Low doses of the NKT cell stimulating αGalCer analog PBS57 applied at the time of infection led to disease exacerbation in C57BL/6 wild-type, but not NKT-deficient mice. The effect was dependent both on the timing and amount of PBS57 administered. The effect of NKT cell stimulation by PBS57 proved to be IL-4 dependent, as it was neutralized in IL-4-deficient C57BL/6 or anti-IL-4 antibody-treated wild-type mice. In contrast to C57BL/6 mice, administration of PBS57 in susceptible BALB/c mice resulted in an improved course of disease. Our results reveal a strain- and cytokine-dependent regulatory role of NKT cells in the development of immunity to low dose L. major infections. These effects, probably masked in previous studies using higher parasite inocula, should be considered in future therapy and immunization approaches.

  3. Pair formation models for sexually transmitted infections: A primer

    Directory of Open Access Journals (Sweden)

    Mirjam Kretzschmar

    2017-08-01

    Full Text Available For modelling sexually transmitted infections, duration of partnerships can strongly influence the transmission dynamics of the infection. If partnerships are monogamous, pairs of susceptible individuals are protected from becoming infected, while pairs of infected individuals delay onward transmission of the infection as long as they persist. In addition, for curable infections re-infection from an infected partner may occur. Furthermore, interventions based on contact tracing rely on the possibility of identifying and treating partners of infected individuals. To reflect these features in a mathematical model, pair formation models were introduced to mathematical epidemiology in the 1980's. They have since been developed into a widely used tool in modelling sexually transmitted infections and the impact of interventions. Here we give a basic introduction to the concepts of pair formation models for a susceptible-infected-susceptible (SIS epidemic. We review some results and applications of pair formation models mainly in the context of chlamydia infection. Keywords: Pair formation, Mathematical model, Partnership duration, Sexually transmitted infections, Basic reproduction number

  4. Dengue human infection model performance parameters.

    Science.gov (United States)

    Endy, Timothy P

    2014-06-15

    Dengue is a global health problem and of concern to travelers and deploying military personnel with development and licensure of an effective tetravalent dengue vaccine a public health priority. The dengue viruses (DENVs) are mosquito-borne flaviviruses transmitted by infected Aedes mosquitoes. Illness manifests across a clinical spectrum with severe disease characterized by intravascular volume depletion and hemorrhage. DENV illness results from a complex interaction of viral properties and host immune responses. Dengue vaccine development efforts are challenged by immunologic complexity, lack of an adequate animal model of disease, absence of an immune correlate of protection, and only partially informative immunogenicity assays. A dengue human infection model (DHIM) will be an essential tool in developing potential dengue vaccines or antivirals. The potential performance parameters needed for a DHIM to support vaccine or antiviral candidates are discussed. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Imunocompetent Mice Model for Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Denise Gonçalves

    2012-01-01

    Full Text Available Dengue fever is a noncontagious infectious disease caused by dengue virus (DENV. DENV belongs to the family Flaviviridae, genus Flavivirus, and is classified into four antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The number of nations and people affected has increased steadily and today is considered the most widely spread arbovirus (arthropod-borne viral disease in the world. The absence of an appropriate animal model for studying the disease has hindered the understanding of dengue pathogenesis. In our study, we have found that immunocompetent C57BL/6 mice infected intraperitoneally with DENV-1 presented some signs of dengue disease such as thrombocytopenia, spleen hemorrhage, liver damage, and increase in production of IFNγ and TNFα cytokines. Moreover, the animals became viremic and the virus was detected in several organs by real-time RT-PCR. Thus, this animal model could be used to study mechanism of dengue virus infection, to test antiviral drugs, as well as to evaluate candidate vaccines.

  6. Animal models for the study of hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    Wei-Na Guo

    2018-01-01

    Full Text Available Even with an effective vaccine, an estimated 240 million people are chronically infected with hepatitis B virus (HBV worldwide. Current antiviral therapies, including interferon and nucleot(side analogues, rarely cure chronic hepatitis B. Animal models are very crucial for understanding the pathogenesis of chronic hepatitis B and developing new therapeutic drugs or strategies. HBV can only infect humans and chimpanzees, with the use of chimpanzees in HBV research strongly restricted. Thus, most advances in HBV research have been gained using mouse models with HBV replication or infection or models with HBV-related hepadnaviral infection. This review summarizes the animal models currently available for the study of HBV infection.

  7. Henipavirus Infections: Lessons from Animal Models

    Directory of Open Access Journals (Sweden)

    Kévin P. Dhondt

    2013-04-01

    Full Text Available The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed.

  8. Perception and acceptance of intradermal influenza vaccination: Patient reported outcomes from phase 3 clinical trials.

    Science.gov (United States)

    Reygrobellet, Camille; Viala-Danten, Muriel; Meunier, Juliette; Weber, Françoise; Nguyen, Van Hung

    2010-04-01

    An intradermal trivalent inactivated influenza vaccine administered using a microinjection system has received European marketing authorization from the European Medicine Agency. We assessed clinical trial subjects' perception of injection site reactions (ISRs) and whether ISRs affected overall acceptability of vaccination and willingness to be vaccinated in the future. A validated, self-administered, patient reported outcome questionnaire was completed 21 days after intradermal or intramuscular vaccination by elderly and non-elderly adult participants in two European randomized, controlled, open-label phase 3 trials. The questionnaire addressed: the acceptability of ISRs, effect of ISRs on arm movement or sleep, satisfaction with the injection system, and willingness to be revaccinated. Questions were answered using a 5-point Likert verbal rating scale (1 = most favourable, 5 = most unfavourable response). Mean scores were calculated per group. 5,305 questionnaires were completed and analysed (95% return rate). Mean scores were close to 1 in all cases (maximum 1.68), indicating an overall favourable opinion of the vaccination and ISRs. More than 96% of participants rated ISRs after intradermal or intramuscular vaccination as either 'totally acceptable' or 'very acceptable'. Willingness to get vaccinated the following year and satisfaction with the intradermal microinjection system or the conventional intramuscular syringe were high and were not adversely affected by ISRs. ISRs after intradermal influenza vaccine administered using a microinjection system are well accepted by the vaccinees and are generally not a cause for concern.

  9. A lung segmental model of chronic Pseudomonas infection in sheep.

    Directory of Open Access Journals (Sweden)

    David Collie

    Full Text Available Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep.Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>10(4 cfu/g.The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches.

  10. A lung segmental model of chronic Pseudomonas infection in sheep.

    Science.gov (United States)

    Collie, David; Govan, John; Wright, Steven; Thornton, Elisabeth; Tennant, Peter; Smith, Sionagh; Doherty, Catherine; McLachlan, Gerry

    2013-01-01

    Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep. Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>10(4) cfu/g). The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches.

  11. Repetitive intradermal bleomycin injections evoke T-helper cell 2 cytokine-driven pulmonary fibrosis.

    Science.gov (United States)

    Singh, Brijendra; Kasam, Rajesh K; Sontake, Vishwaraj; Wynn, Thomas A; Madala, Satish K

    2017-11-01

    IL-4 and IL-13 are major T-helper cell (Th) 2 cytokines implicated in the pathogenesis of several lung diseases, including pulmonary fibrosis. In this study, using a novel repetitive intradermal bleomycin model in which mice develop extensive lung fibrosis and a progressive decline in lung function compared with saline-treated control mice, we investigated profibrotic functions of Th2 cytokines. To determine the role of IL-13 signaling in the pathogenesis of bleomycin-induced pulmonary fibrosis, wild-type, IL-13, and IL-4Rα-deficient mice were treated with bleomycin, and lungs were assessed for changes in lung function and pulmonary fibrosis. Histological staining and lung function measurements demonstrated that collagen deposition and lung function decline were attenuated in mice deficient in either IL-13 or IL-4Rα-driven signaling compared with wild-type mice treated with bleomycin. Furthermore, our results demonstrated that IL-13 and IL-4Rα-driven signaling are involved in excessive migration of macrophages and fibroblasts. Notably, our findings demonstrated that IL-13-driven migration involves increased phospho-focal adhesion kinase signaling and F-actin polymerization. Importantly, in vivo findings demonstrated that IL-13 augments matrix metalloproteinase (MMP)-2 and MMP9 activity that has also been shown to increase migration and invasiveness of fibroblasts in the lungs during bleomycin-induced pulmonary fibrosis. Together, our findings demonstrate a pathogenic role for Th2-cytokine signaling that includes excessive migration and protease activity involved in severe fibrotic lung disease.

  12. Severe acute caffeine poisoning due to intradermal injections: Mesotherapy hazard

    Directory of Open Access Journals (Sweden)

    Perković-Vukčević Nataša

    2012-01-01

    Full Text Available Introduction. Caffeine is indicated in the treatment of migraine headaches, as well as neonatal apnea and bradycardia syndrome. In mild poisoning, the most prevalent symptoms are nausea, vomiting, diarrhea, tremor, anxiety and headache. In more severe cases, symptoms consist of heart rythym abnormalities, myocardial infarction and seizures. Due to its common lipolytic effect, caffeine is used in mesotherapy, usually in combination with drugs of similar effect. We presented a patient with acute iatrogenic caffeine poisoning. Case report. A 51-year-old woman, with preexisting hypertension and hypertensive cardiomyopathy was subjected to cosmetic treatment in order to remove fat by intradermal caffeine injections. During the treatment the patient felt sickness, an urge to vomit, and a pronounced deterioration of general condition. Upon examination, the patient exhibited somnolence, hypotension and nonsustained ventricular tachycardia, which was sufficient enough evidence for further hospitalization. On admission to the intensive care unit the patient was anxious with increased heart rate, normotensive, with cold, damp skin, and visible traces of injection sites with surrounding hematomas on the anterior abdominal wall. Paroxysmal supraventricular tachycardia (PSVT on electrocardiographic monitoring was found. The laboratory analysis determined a lowered potassium level of 2.1 mmol/L (normal range 3,5 - 5.2 mmol/L, and a toxicological analysis (liquid chromatography with ultraviolet detection proved a toxic concentration of caffeine in plasma - 85.03 mg/L (toxic concentration over 25 mg/L. On application of intensive therapy, antiarrhythmics, and substitution of potassium, as well as both symptomatic and supportive therapy, there was a significant recovery. The patient was discharged without any sequele within four days. Conclusion. A presented rare iatrogenic acute caffeine poisoning occured due to massive absorption of caffeine from the

  13. Natural Gastric Infection with Helicobacter pylori in Monkeys: A Model for Spiral Bacteria Infection in Humans

    Science.gov (United States)

    1994-01-01

    Schoenknecht FD. Campytobacter pyloni isolated of H. pyfon from human faeces . Lancet 1992:340:1194-1195. from the stomachg of the monkey Maca nemestnina. J Clin...Helicobacter pylori in Monkeys: A Model for Spiral Bacteria Infection in Humans ANDRE DUBOIS,*’t NANCY FIALA,*’` LILLIE M. HEMAN-ACKAH,% E. SUSAN DRAZEK...model for Helicobacter pyloi Infection In humans . The of this infection has been primarily based on identifica- aim of this study was to examine the

  14. Intradermal invasive lobular carcinoma presenting: Not everything in the skin is benign.

    Science.gov (United States)

    Eaton, Jennifer Wells; Drotman, Michele B; Sales, Rachel M; Arleo, Elizabeth Kagan

    In this case report, the history and imaging of two patients with invasive lobular carcinoma (ILC) in the skin are presented, followed by a discussion of both benign and malignant intradermal findings on breast ultrasound. Although the majority of dermal findings are benign, these cases are a reminder that malignancy can manifest within the skin. The purpose of presenting these cases together is to remind breast imagers of the importance of considering malignancy in the differential diagnosis of intradermal lesions on breast ultrasound, especially in special circumstances such as a personal history of breast cancer or associated clinical findings. Copyright © 2017. Published by Elsevier Inc.

  15. Dynamics of delayed pathogen infection models with pathogenic and cellular infections and immune impairment

    Science.gov (United States)

    Elaiw, A. M.; Raezah, A. A.; Alofi, B. S.

    2018-02-01

    We study the global dynamics of delayed pathogen infection models with immune impairment. Both pathogen-to-susceptible and infected-to-susceptible transmissions have been considered. Bilinear and saturated incidence rates are considered in the first and second model, respectively. We drive the basic reproduction parameter R0 which determines the global dynamics of models. Using Lyapunov method, we established the global stability of the models' steady states. The theoretical results are confirmed by numerical simulations.

  16. A Discrete Model for HIV Infection with Distributed Delay

    Directory of Open Access Journals (Sweden)

    Brahim EL Boukari

    2014-01-01

    Full Text Available We give a consistent discretization of a continuous model of HIV infection, with distributed time delays to express the lag between the times when the virus enters a cell and when the cell becomes infected. The global stability of the steady states of the model is determined and numerical simulations are presented to illustrate our theoretical results.

  17. A model of immunomodulatory for dengue infection mm

    Science.gov (United States)

    Zulfa, Annisa; Handayani, Dewi; Nuraini, Nuning

    2018-03-01

    An immunomodulatory model for dengue infection is constructed in this paper. This study focuses on T-cell compartments and B cells that are immune cells involved in the dengue infection process. Dengue virus-infected monocyte cells release interferons to signal T-cells to activate B-cells and produce antibodies. Immunomodulator acts as a treatment control and aims to increase the numbers of antibodies so it is expected to reduce the number of infected monocyte cells by dengue virus. Numerical simulation shows that the greater the rate of f (t) the immune cells will be stimulated to suppress the number of infected cells.

  18. MyD88-dependent immunity to a natural model of vaccinia virus infection does not involve Toll-like receptor 2.

    Science.gov (United States)

    Davies, Michael L; Sei, Janet J; Siciliano, Nicholas A; Xu, Ren-Huan; Roscoe, Felicia; Sigal, Luis J; Eisenlohr, Laurence C; Norbury, Christopher C

    2014-03-01

    Although the pattern recognition receptor Toll-like receptor 2 (TLR2) is typically thought to recognize bacterial components, it has been described to alter the induction of both innate and adaptive immunity to a number of viruses, including vaccinia virus (VACV). However, many pathogens that reportedly encode TLR2 agonists may actually be artifactually contaminated during preparation, possibly with cellular debris or merely with molecules that sensitize cells to be activated by authentic TLR2 agonists. In both humans and mice, the most relevant natural route of infection with VACV is through intradermal infection of the skin. Therefore, we examined the requirement for TLR2 and its signaling adaptor MyD88 in protective immunity to VACV after intradermal infection. We find that although TLR2 may recognize virus preparations in vitro and have a minor role in preventing dissemination of VACV following systemic infection with large doses of virus, it is wholly disposable in both control of virus replication and induction of adaptive immunity following intradermal infection. In contrast, MyD88 is required for efficient induction of CD4 T cell and B cell responses and for local control of virus replication following intradermal infection. However, even MyD88 is not required to induce local inflammation, inflammatory cytokine production, or recruitment of cells that restrict virus from spreading systemically after peripheral infection. Thus, an effective antiviral response does require MyD88, but TLR2 is not required for control of a peripheral VACV infection. These findings emphasize the importance of studying relevant routes of infection when examining innate sensing mechanisms. Vaccinia virus (VACV) provides the backbone for some of the most widely used and successful viral vaccine vectors and is also related to the human pathogens Cantagalo virus and molluscum contagiosum virus that infect the skin of patients. Therefore, it is vital to understand the mechanisms that

  19. Lysozyme, intradermal diffusion of india ink and peritoneal capillary permeability in mice.

    Science.gov (United States)

    Bianchi, C; Goi, A; Ronchini, A

    1982-04-01

    Hen egg white lysozyme injected intracutaneously into mice inhibits the intradermal diffusion of India Ink. The effect of lysozyme persists in presence of hyaluronidase. Lysozyme injected i.p. into mice inhibits acetic acid (i.p.) induced leakage of Pontamine Sky Blue into the abdominal cavity. The data suggest that lysozyme might be tried for applications outside the microbiological field.

  20. Sentinel node localization in breast cancer patients using intradermal dye injection

    DEFF Research Database (Denmark)

    Ilum, Lars; Bak, Martin; Olsen, K E

    2000-01-01

    In a series of 161 consecutive breast cancer operations, intradermal injection of Patent Blue was used to localize the sentinel node (SN). The surgical localization rate was 60%. Including the blue lymph nodes found by the pathologist, localization rate was 70%. After the first 103 operations, th...

  1. Syndecan-1 is required to maintain intradermal fat and prevent cold stress.

    Directory of Open Access Journals (Sweden)

    Ildiko Kasza

    2014-08-01

    Full Text Available Homeostatic temperature regulation is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and nervous regulators. Here, we report that loss of the heparan sulfate proteoglycan, syndecan-1, causes a profoundly depleted intradermal fat layer, which provides crucial thermogenic insulation for mammals. Mice without syndecan-1 enter torpor upon fasting and show multiple indicators of cold stress, including activation of the stress checkpoint p38α in brown adipose tissue, liver and lung. The metabolic phenotype in mutant mice, including reduced liver glycogen, is rescued by housing at thermoneutrality, suggesting that reduced insulation in cool temperatures underlies the observed phenotypes. We find that syndecan-1, which functions as a facultative lipoprotein uptake receptor, is required for adipocyte differentiation in vitro. Intradermal fat shows highly dynamic differentiation, continuously expanding and involuting in response to hair cycle and ambient temperature. This physiology probably confers a unique role for Sdc1 in this adipocyte sub-type. The PPARγ agonist rosiglitazone rescues Sdc1-/- intradermal adipose tissue, placing PPARγ downstream of Sdc1 in triggering adipocyte differentiation. Our study indicates that disruption of intradermal adipose tissue development results in cold stress and complex metabolic pathology.

  2. Ag coated microneedle based surface enhanced Raman scattering probe for intradermal measurements

    Science.gov (United States)

    Yuen, Clement; Liu, Quan

    2013-06-01

    We propose a silver coated microneedle to detect test molecules, including R6G and glucose, positioned at a depth of more than 700 μm below a skin phantom surface for mimicking intradermal surface-enhanced Raman scattering measurements.

  3. The Intradermal Tuberculin Test as a Research Tool | De Ville De ...

    African Journals Online (AJOL)

    Epidemiological studies and controlled comparative trials in tuberculosis require precise measurement of delayed hypersensitivity to tuberculin, and only the intradermal test can provide this accuracy. The correct procedures for random sampling, random allocation of treatments and blindness of assessment are discussed.

  4. Mouse models of acute and chronic hepacivirus infection

    DEFF Research Database (Denmark)

    Billerbeck, Eva; Wolfisberg, Raphael; Fahnøe, Ulrik

    2017-01-01

    An estimated 71 million people worldwide are infected with hepatitis C virus (HCV). The lack of small-animal models has impeded studies of antiviral immune mechanisms. Here we show that an HCV-related hepacivirus discovered in Norway rats can establish high-titer hepatotropic infections in labora......An estimated 71 million people worldwide are infected with hepatitis C virus (HCV). The lack of small-animal models has impeded studies of antiviral immune mechanisms. Here we show that an HCV-related hepacivirus discovered in Norway rats can establish high-titer hepatotropic infections...... provide mechanistic insights into hepatic antiviral immunity, a prerequisite for the development of HCV vaccines....

  5. Enterococcus infection biology: lessons from invertebrate host models.

    Science.gov (United States)

    Yuen, Grace J; Ausubel, Frederick M

    2014-03-01

    The enterococci are commensals of the gastrointestinal tract of many metazoans, from insects to humans. While they normally do not cause disease in the intestine, they can become pathogenic when they infect sites outside of the gut. Recently, the enterococci have become important nosocomial pathogens, with the majority of human enterococcal infections caused by two species, Enterococcus faecalis and Enterococcus faecium. Studies using invertebrate infection models have revealed insights into the biology of enterococcal infections, as well as general principles underlying host innate immune defense. This review highlights recent findings on Enterococcus infection biology from two invertebrate infection models, the greater wax moth Galleria mellonella and the free-living bacteriovorous nematode Caenorhabditis elegans.

  6. Modelling the contact propagation of nosocomial infection in emergency departments

    OpenAIRE

    Jaramillo, Cecilia; Taboada, Manel; Epelde, Francisco; Rexachs, Dolores; Luque Amat, Emilio

    2015-01-01

    The nosocomial infection is a special kind of infection that is caused by microorganisms acquired inside a hospital. In the daily care process of an emergency department, the interactions between patients and sanitary staff create the environment for the transmission of such microorganisms. Rates of morbility and mortality due to nosocomial infections areimportant indicators of the quality of hospital work. In this research, we use Agent Based Modeling and Simulation tech...

  7. Intradermal and virosomal influenza vaccines for preventing influenza hospitalization in the elderly during the 2011-2012 influenza season: a comparative effectiveness study using the Valencia health care information system.

    Science.gov (United States)

    Puig-Barberà, J; Natividad-Sancho, A; Calabuig-Pérez, J; Lluch-Rodrigo, J A; Pastor-Villalba, E; Martínez-Úbeda, S; Díez-Domingo, J

    2014-09-22

    The use of intradermal vaccination or virosomal vaccines could increase protection against influenza among the vulnerable population of older adults. Studies assessing the comparative effectiveness of these two influenza vaccine types in this age group are lacking. We conducted a retrospective cohort study to estimate the comparative effectiveness of intradermal seasonal trivalent-influenza vaccine (TIV) delivered by a microneedle injection system and a virosomal-TIV intramuscularly delivered for prevention of influenza hospitalization in non-institutionalized adults aged ≥65 years. We obtained administrative data on immunization status and influenza hospitalization for the 2011-2012 influenza season, and used Cox regression models to assess comparative effectiveness. We estimated crude and adjusted (age, sex, comorbidity, pharmaceutical claims, recent pneumococcal vaccination and number of hospitalizations for all causes other than influenza between the previous and current influenza seasons) hazard ratios (HR). Overall, 164,021 vaccinated subjects were evaluated. There were 127 hospitalizations for influenza among 62,058 subjects, contributing 914,740 person-weeks at risk in the virosomal-TIV group, and 133 hospitalizations for influenza among 101,963 subjects, contributing 1,504,570 person-weeks at risk in the intradermal-TIV group. The crude HR of intradermal-TIV relative to virosomal-TIV was 0.64 (95% confidence interval (CI): 0.50-0.81), and the adjusted Cox estimated HR was 0.67 (95% CI: 0.52-0.85). During the 2011-2012 influenza season the risk of hospitalization for influenza was reduced by 33% in non-institutionalized elderly adults who were vaccinated with intradermal-TIV compared with virosomal-TIV. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Advances in Animal Models of Hepatitis B Virus Infection

    Directory of Open Access Journals (Sweden)

    Zhang Hang

    2015-12-01

    Full Text Available Hepatitis B virus (HBV infection seriously affects human health. Stable and reliable animal models of HBV infection bear significance in studying pathogenesis of this health condition and development of intervention measures. HBV exhibits high specificity for hosts, and chimpanzee is long used as sole animal model of HBV infection. However, use of chimpanzees is strictly constrained because of ethical reasons. Many methods were used to establish small-animal models of HBV infection. Tupaia is the only nonprimate animal that can be infected by HBV. Use of HBV-related duck hepatitis virus and marmot hepatitis virus infection model contributed to evaluation of mechanism of HBV replication and HBV treatment methods. In recent years, development of human–mouse chimeric model provided possibility of using common experimental animals to carry out HBV research. These models feature their own advantages and disadvantages and can be complementary in some ways. This study provides an overview of current and commonly used animal models of HBV infection.

  9. Mathematical modelling : a tool for hospital infection control

    NARCIS (Netherlands)

    Grundmann, H; Hellriegel, B

    Health-care-associated infections caused by antibiotic-resistant pathogens have become a menace in hospitals worldwide and infection control measures have lead to vastly different outcomes in different countries. During the past 6 years, a theoretical framework based on mathematical models has

  10. Mathematical modelling: a tool for hospital infection control

    NARCIS (Netherlands)

    Grundmann, Hajo; Hellriegel, B.

    2006-01-01

    Health-care-associated infections caused by antibiotic-resistant pathogens have become a menace in hospitals worldwide and infection control measures have lead to vastly different outcomes in different countries. During the past 6 years, a theoretical framework based on mathematical models has

  11. Mathematical modelling: a tool for hospital infection control.

    NARCIS (Netherlands)

    Grundmann, Hajo; Hellriegel, B

    2006-01-01

    Health-care-associated infections caused by antibiotic-resistant pathogens have become a menace in hospitals worldwide and infection control measures have lead to vastly different outcomes in different countries. During the past 6 years, a theoretical framework based on mathematical models has

  12. Modeling Influenza Virus Infection: A Roadmap for Influenza Research

    Directory of Open Access Journals (Sweden)

    Alessandro Boianelli

    2015-10-01

    Full Text Available Influenza A virus (IAV infection represents a global threat causing seasonal outbreaks and pandemics. Additionally, secondary bacterial infections, caused mainly by Streptococcus pneumoniae, are one of the main complications and responsible for the enhanced morbidity and mortality associated with IAV infections. In spite of the significant advances in our knowledge of IAV infections, holistic comprehension of the interplay between IAV and the host immune response (IR remains largely fragmented. During the last decade, mathematical modeling has been instrumental to explain and quantify IAV dynamics. In this paper, we review not only the state of the art of mathematical models of IAV infection but also the methodologies exploited for parameter estimation. We focus on the adaptive IR control of IAV infection and the possible mechanisms that could promote a secondary bacterial coinfection. To exemplify IAV dynamics and identifiability issues, a mathematical model to explain the interactions between adaptive IR and IAV infection is considered. Furthermore, in this paper we propose a roadmap for future influenza research. The development of a mathematical modeling framework with a secondary bacterial coinfection, immunosenescence, host genetic factors and responsiveness to vaccination will be pivotal to advance IAV infection understanding and treatment optimization.

  13. Immunotherapy in viral warts with intradermal Bacillus Calmette–Guerin vaccine versus intradermal tuberculin purified protein derivative: A double-blind, randomized controlled trial comparing effectiveness and safety in a tertiary care center in Eastern India

    Directory of Open Access Journals (Sweden)

    Indrashis Podder

    2017-01-01

    Conclusion: Both intradermal Bacillus Calmette–Guerin and tuberculin purified protein derivative hold promise in the treatment of viral warts. Bacillus Calmette–Guerin may be more effective, though it had more adverse events in our study.

  14. Animal models for the study of Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    Eliza Miszczyk

    2014-05-01

    Full Text Available The Gram-negative bacillus Helicobacter pylori is widely recognized as a major etiologic agent responsible for chronic active gastritis, peptic ulcers, the development of gastric cancer and mucosa-associated lymphoid tissue (MALT lymphoma. Still, little is known about the natural history of H. pylori infection, since patients usually after many years of not suffering from symptoms of the infection are simply asymptomatic. Since the research investigators carried out on human models has many limitations, there is an urgent need for the development of an animal model optimal and suitable for the monitoring of H. pylori infections. This review summarizes the recent findings on the suitability of animal models used in H. pylori research. Several animal models are useful for the assessment of pathological, microbiological and immunological consequences of infection, which makes it possible to monitor the natural

  15. Modeling Innate Immune Response to Early Mycobacterium Infection

    Directory of Open Access Journals (Sweden)

    Rafael V. Carvalho

    2012-01-01

    Full Text Available In the study of complex patterns in biology, mathematical and computational models are emerging as important tools. In addition to experimental approaches, these modeling tools have recently been applied to address open questions regarding host-pathogen interaction dynamics, including the immune response to mycobacterial infection and tuberculous granuloma formation. We present an approach in which a computational model represents the interaction of the Mycobacterium infection with the innate immune system in zebrafish at a high level of abstraction. We use the Petri Net formalism to model the interaction between the key host elements involved in granuloma formation and infection dissemination. We define a qualitative model for the understanding and description of causal relations in this dynamic process. Complex processes involving cell-cell or cell-bacteria communication can be modeled at smaller scales and incorporated hierarchically into this main model; these are to be included in later elaborations. With the infection mechanism being defined on a higher level, lower-level processes influencing the host-pathogen interaction can be identified, modeled, and tested both quantitatively and qualitatively. This systems biology framework incorporates modeling to generate and test hypotheses, to perform virtual experiments, and to make experimentally verifiable predictions. Thereby it supports the unraveling of the mechanisms of tuberculosis infection.

  16. Increased Sensitization to Mold Allergens Measured by Intradermal Skin Testing following Hurricanes.

    Science.gov (United States)

    Saporta, Diego; Hurst, David

    2017-01-01

    Objective . To report on changes in sensitivity to mold allergens determined by changes in intradermal skin testing reactivity, after exposure to two severe hurricanes. Methods . A random, retrospective allergy charts review divided into 2 groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior to hurricanes, and Group B, patients tested in 2014 and 2015 following hurricanes. Reactivity to eighteen molds was determined by intradermal skin testing. Test results, age, and respiratory symptoms were recorded. Chi-square test determined reactivity/sensitivity differences between groups. Results . Posthurricane patients had 34.6 times more positive results ( p hurricanes ( p hurricanes ( p hurricanes. This supports climatologists' hypothesis that environmental changes resulting from hurricanes can be a health risk as reflected in increased allergic sensitivities and symptoms and has significant implications for physicians treating patients from affected areas.

  17. Common allergens of atopic dermatitis in dogs: comparative findings based on intradermal tests

    Science.gov (United States)

    Kim, Ha-Jung; Kang, Min-Hee

    2011-01-01

    Intradermal tests were performed on 58 dogs diagnosed with atopic dermatitis from 2004~2008 at the Veterinary Medical Teaching Hospital of Konkuk University, Korea. To compare the allergen distribution observed in the present investigation to the results from other studies conducted in Korea and elsewhere, the allergens were grouped according to their kinds. There was no significant difference in gender distribution among the dogs. The most common breeds among the 58 dogs were Maltese (n = 11) and Shih-tzu (n = 11). The average age was 4.8 years. The most frequently produced a positive reaction on the intradermal tests was mold (67.3%) followed by house dust (54.5%) and house dust mites (49.1%). The present study found a low distribution of dogs allergic to various outdoor allergens compared to studies performed in other countries; this may reflect differences in living conditions for dogs living in Korea. PMID:21897103

  18. Aero-allergens in canine atopic dermatitis in southeastern Australia based on 1000 intradermal skin tests.

    Science.gov (United States)

    Mueller, R S; Bettenay, S V; Tideman, L

    2000-06-01

    To determine the most relevant aero-allergens involved in canine atopic dermatitis in southeastern Australia and provide information about these aero-allergens to the general practitioner. Dogs presented to the Animal Skin & Allergy Clinic with history and clinical signs of atopic dermatitis were injected intradermally with 38 different allergens and negative and positive control. Intradermal skin tests in 1000 dogs were retrospectively evaluated. One third of all patients reacted to the house dust mite Dermatophagoides farinae. Allergens reacting in more than 15% of the patients were wheat (Triticum aestivum), sweet vernal (Anthoxanthum odoratum), English couch (Agropyron repens), yellow dock (Rumex crispus), Mexican tea (Chenopodium ambrosioides), plantain (Plantago lanceolata), melaleuca (Melaleuca quinquenervia) and peppercorn (Schimus spp). House dust mites are the most common allergens in canine atopic dermatitis in southeastern Australia and D farinae is involved most frequently. However, a number of grass, weed and tree pollens also are involved regularly.

  19. Application of a topical vapocoolant spray decreases pain at the site of initial intradermal anaesthetic injection during ultrasound-guided breast needle biopsy

    International Nuclear Information System (INIS)

    Collado-Mesa, F.; Net, J.M.; Arheart, K.; Klevos, G.A.; Yepes, M.M.

    2015-01-01

    Aim: To assess whether the application of a topical vapocoolant spray immediately prior to initial intradermal anaesthetic injection during ultrasound-guided breast biopsy decreases pain at the site of the initial injection. Materials and methods: In this institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study, 50 women aged 49.1 ± 1.6 years (mean ± standard error) were recruited and provided written informed consent. Participants served as their own controls and were blinded as to whether a topical vapocoolant spray or a placebo was used immediately prior to the initial local anaesthetic injection at two separate biopsy sites. With the exception of the application of vapocoolant or placebo, the entire ultrasound-guided procedure was performed according to a routine protocol. Participants recorded pain at initial injection site on a visual analogue scale. General linear mixed models for repeated measures analysis of variance and a 0.05 significance level were used. Results: Application of topical vapocoolant spray was shown to significantly decrease pain at the site of initial intradermal anaesthetic injection as compared to placebo (p<0.001). Treatment effect was independent of age of the subject, race/ethnicity, operator, type of biopsy device, and histopathology result. No complications from vapocoolant spray use were reported. Conclusion: Application of a topical vapocoolant spray immediately prior to initial intradermal anaesthetic injection during ultrasound-guided breast biopsy significantly decreases pain at the site of the initial injection and could contribute to improve the patient's overall procedural experience. -- Highlights: •Topical vapocoolant spray decreased pain at site of initial anesthetic injection (

  20. Intradermal Infiltration of Local Anesthetic?Rapid and Bloodless Deepithelialization of the Breast Pedicle

    OpenAIRE

    Bennett, Katelyn G.; Gilman, Robert H.

    2017-01-01

    Summary: Breast reduction is one of the most commonly performed plastic surgery procedures, and pedicle deepithelialization remains a time-consuming step of the operation. This is especially true when using an inferior pedicle. We present a novel technique of intradermal infiltration of the breast pedicle with local anesthetic to facilitate efficient, bloodless deepithelialization. The senior author uses a 20-ml syringe to inject 0.25% lidocaine and 1:400,000 epinephrine just beneath the epid...

  1. Cross-Linked Fluorescent Supramolecular Nanoparticles as Finite Tattoo Pigments with Controllable Intradermal Retention Times.

    Science.gov (United States)

    Choi, Jin-Sil; Zhu, Yazhen; Li, Hongsheng; Peyda, Parham; Nguyen, Thuy Tien; Shen, Mo Yuan; Yang, Yang Michael; Zhu, Jingyi; Liu, Mei; Lee, Mandy M; Sun, Shih-Sheng; Yang, Yang; Yu, Hsiao-Hua; Chen, Kai; Chuang, Gary S; Tseng, Hsian-Rong

    2017-01-24

    Tattooing has been utilized by the medical community for precisely demarcating anatomic landmarks. This practice is especially important for identifying biopsy sites of nonmelanoma skin cancer (NMSC) due to the long interval (i.e., up to 3 months) between the initial diagnostic biopsy and surgical treatment. Commercially available tattoo pigments possess several issues, which include causing poor cosmesis, being mistaken for a melanocytic lesion, requiring additional removal procedures when no longer desired, and potentially inducing inflammatory responses. The ideal tattoo pigment for labeling of skin biopsy sites for NMSC requires (i) invisibility under ambient light, (ii) fluorescence under a selective light source, (iii) a finite intradermal retention time (ca. 3 months), and (iv) biocompatibility. Herein, we introduce cross-linked fluorescent supramolecular nanoparticles (c-FSNPs) as a "finite tattoo" pigment, with optimized photophysical properties and intradermal retention time to achieve successful in vivo finite tattooing. Fluorescent supramolecular nanoparticles encapsulate a fluorescent conjugated polymer, poly[5-methoxy-2-(3-sulfopropoxy)-1,4-phenylenevinylene] (MPS-PPV), into a core via a supramolecular synthetic approach. FSNPs which possess fluorescent properties superior to those of the free MPS-PPV are obtained through a combinatorial screening process. Covalent cross-linking of FSNPs results in micrometer-sized c-FSNPs, which exhibit a size-dependent intradermal retention. The 1456 nm sized c-FSNPs display an ideal intradermal retention time (ca. 3 months) for NMSC lesion labeling, as observed in an in vivo tattoo study. In addition, the c-FSNPs induce undetectable inflammatory responses after tattooing. We believe that the c-FSNPs can serve as a "finite tattoo" pigment to label potential malignant NMSC lesions.

  2. Interrupted or continuous-intradermal suturing? Statistical analysis of postoperative scars

    Directory of Open Access Journals (Sweden)

    Elif Sarı

    2014-12-01

    Full Text Available Background and Design: Postoperative scar development is an important problem for patients treated in plastic surgery clinics. Most patients think that continuous intradermal suturing is superior to interrupted suturing because they assume that it creates less scarring. We evaluated scars that form following intradermal and interrupted suturing. This article presents our controlled study that objectively compared the scars on patients' faces using a wound evaluation scale. Materials and Methods: Thirty-five patients, who had undergone operations on the bilateral cheeks, were included in this study. Thirty patients were female; five patients were male. Their mean age was 40.05 years. The average scar evaluation time after surgery was 9.05 months. Elliptical excisions were made on the lesions under local anesthesia. The incisions on the right cheeks were sutured with 6/0 monofilament nonabsorbable sutures using the continuous intradermal suturing technique. The left cheek incisions were sutured with same sutures using the interrupted suturing method. Results: The patients were evaluated 7–11 months after operation (mean: 9.05 months using the Stony Brook Scar Evaluation Scale. A Related Samples T-test was used for statistical evaluation of the differences between the suturing techniques. No significant differences were noted in scar formation between the two suturing methods (p>0.05. Conclusion: We found no differences in scar formation between the two frequently used suturing techniques studied here. We believe that the suturing technique is a less important determinant of scar formation than are other factors.

  3. The host model Galleria mellonella is resistant to taylorellae infection.

    Science.gov (United States)

    Hébert, L; Rincé, I; Sanna, C; Laugier, C; Rincé, A; Petry, S

    2014-10-01

    The genus Taylorella is composed of two species: (i) Taylorella equigenitalis, the causative agent of CEM, a venereally transmitted infection of Equidae and (ii) Taylorella asinigenitalis, a closely related species considered to be nonpathogenic, although experimental infection of mares with this bacterium resulted in clinical signs of vaginitis, cervicitis or endometritis. Currently, there is a need for an alternative host model to further study the taylorellae species. In this context, we explored Galleria mellonella larvae as potential alternative model hosts for taylorellae. Our results showed that infection of G. mellonella larvae with a high concentration of taylorellae did not induce overt G. mellonella mortality and that taylorellae were not able to proliferate within G. mellonella. In conclusion, G. mellonella larvae are resistant to taylorellae infection and therefore do not constitute a relevant alternative system for studying the virulence of taylorellae species. Significance and impact of the study: To date, the pathogenicity and host colonization capacity of Taylorella equigenitalis, the causative agent of contagious equine metritis (CEM) and T. asinigenitalis, the second species within the Taylorella genus, remain largely unknown. In this study, we evaluated the relevance of Galleria mellonella as an infection model for taylorellae; we showed that G. mellonella are resistant to taylorellae infection and therefore do not constitute a suitable host model for taylorellae. © 2014 The Society for Applied Microbiology.

  4. Improved hidden Markov model for nosocomial infections.

    Science.gov (United States)

    Khader, Karim; Leecaster, Molly; Greene, Tom; Samore, Matthew; Thomas, Alun

    2014-12-01

    We propose a novel hidden Markov model (HMM) for parameter estimation in hospital transmission models, and show that commonly made simplifying assumptions can lead to severe model misspecification and poor parameter estimates. A standard HMM that embodies two commonly made simplifying assumptions, namely a fixed patient count and binomially distributed detections is compared with a new alternative HMM that does not require these simplifying assumptions. Using simulated data, we demonstrate how each of the simplifying assumptions used by the standard model leads to model misspecification, whereas the alternative model results in accurate parameter estimates. © The Authors 2013. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  5. Cohabitation reaction-diffusion model for virus focal infections

    Science.gov (United States)

    Amor, Daniel R.; Fort, Joaquim

    2014-12-01

    The propagation of virus infection fronts has been typically modeled using a set of classical (noncohabitation) reaction-diffusion equations for interacting species. However, for some single-species systems it has been recently shown that noncohabitation reaction-diffusion equations may lead to unrealistic descriptions. We argue that previous virus infection models also have this limitation, because they assume that a virion can simultaneously reproduce inside a cell and diffuse away from it. For this reason, we build a several-species cohabitation model that does not have this limitation. Furthermore, we perform a sensitivity analysis for the most relevant parameters of the model, and we compare the predicted infection speed with observed data for two different strains of the T7 virus.

  6. In Vivo Modeling of Biofilm-Infected Wounds: A Review

    Science.gov (United States)

    2012-07-15

    with the bacterial biofilm (e.g., lung mucosa in association with cystic fibrosis ) [10,11,22,69e71]. In addition, infections in foreign materials such...predicament of cystic fibrosis patients. Trends Microbiol 2000;8:247. [72] Darouiche RO. Treatment of infections associated with surgical implants. N Engl...chronic wound diagnosis . However, similar to previously discussed models, there was no assessment of the wound healing impairment or host inflammatory

  7. Evaluation of non-inferiority of intradermal versus adjuvanted seasonal influenza vaccine using two serological techniques: a randomised comparative study

    Directory of Open Access Journals (Sweden)

    Thomas Stéphane

    2010-05-01

    Full Text Available Abstract Background Although seasonal influenza vaccine is effective in the elderly, immune responses to vaccination are lower in the elderly than in younger adults. Strategies to optimise responses to vaccination in the elderly include using an adjuvanted vaccine or using an intradermal vaccination route. The immunogenicity of an intradermal seasonal influenza vaccine was compared with that of an adjuvanted vaccine in the elderly. Methods Elderly volunteers (age ≥ 65 years were randomised to receive a single dose of trivalent seasonal influenza vaccine: either a split-virion vaccine containing 15 μg haemagglutinin [HA]/strain/0.1-ml dose administered intradermally, or a subunit vaccine (15 μg HA/strain/0.5-ml dose adjuvanted with MF59C.1 and administered intramuscularly. Blood samples were taken before and 21 ± 3 days post-vaccination. Anti-HA antibody titres were assessed using haemagglutination inhibition (HI and single radial haemolysis (SRH methods. We aimed to show that the intradermal vaccine was non-inferior to the adjuvanted vaccine. Results A total of 795 participants were enrolled (intradermal vaccine n = 398; adjuvanted vaccine n = 397. Non-inferiority of the intradermal vaccine was demonstrated for the A/H1N1 and B strains, but not for the A/H3N2 strain (upper bound of the 95% CI = 1.53 using the HI method, and for all three strains by the SRH method. A post-hoc analysis of covariance to adjust for baseline antibody titres demonstrated the non-inferiority of the intradermal vaccine by HI and SRH methods for all three strains. Both vaccines were, in general, well tolerated; the incidence of injection-site reactions was higher for the intradermal (70.1% than the adjuvanted vaccine (33.8% but these reactions were mild and of short duration. Conclusions The immunogenicity and safety of the intradermal seasonal influenza vaccine in the elderly was comparable with that of the adjuvanted vaccine. Intradermal vaccination to target the

  8. Multiscale model for pedestrian and infection dynamics during air travel

    Science.gov (United States)

    Namilae, Sirish; Derjany, Pierrot; Mubayi, Anuj; Scotch, Mathew; Srinivasan, Ashok

    2017-05-01

    In this paper we develop a multiscale model combining social-force-based pedestrian movement with a population level stochastic infection transmission dynamics framework. The model is then applied to study the infection transmission within airplanes and the transmission of the Ebola virus through casual contacts. Drastic limitations on air-travel during epidemics, such as during the 2014 Ebola outbreak in West Africa, carry considerable economic and human costs. We use the computational model to evaluate the effects of passenger movement within airplanes and air-travel policies on the geospatial spread of infectious diseases. We find that boarding policy by an airline is more critical for infection propagation compared to deplaning policy. Enplaning in two sections resulted in fewer infections than the currently followed strategy with multiple zones. In addition, we found that small commercial airplanes are better than larger ones at reducing the number of new infections in a flight. Aggregated results indicate that passenger movement strategies and airplane size predicted through these network models can have significant impact on an event like the 2014 Ebola epidemic. The methodology developed here is generic and can be readily modified to incorporate the impact from the outbreak of other directly transmitted infectious diseases.

  9. The susceptible-infected-recovered (SIR) model for viral marketing

    Science.gov (United States)

    Ismail, Siti Suhaila; Akil, Ku Azlina Ku; Chulan, Majdah; Sharif, Noorzila

    2017-11-01

    Viral marketing is a marketing strategy utilizes social media to spread information about a product or services provided. It is the most powerful way to share information in a short amount of time. The objective of this study is to investigate the dynamic of viral marketing within a time duration in the point of view of mathematics. This study used the epidemiological model known as Susceptible-Infected-Recovered (SIR). The model consists of a system of three differential equations with three state variables namely susceptible (S), infected (I) and recovered (R). It considers a case of SIR model with demography. Numerical experiments have been performed. The results show that viral marketing reaches its peak within two days. The online messages shared will become higher if the initial number of the infected individual has been increased.

  10. Trichuris muris: a model of gastrointestinal parasite infection.

    Science.gov (United States)

    Klementowicz, Joanna E; Travis, Mark A; Grencis, Richard K

    2012-11-01

    Infection with soil-transmitted gastrointestinal parasites, such as Trichuris trichiura, affects more than a billion people worldwide, causing significant morbidity and health problems especially in poverty-stricken developing countries. Despite extensive research, the role of the immune system in triggering parasite expulsion is incompletely understood which hinders the development of anti-parasite therapies. Trichuris muris infection in mice serves as a useful model of T. trichiura infection in humans and has proven to be an invaluable tool in increasing our understanding of the role of the immune system in promoting either susceptibility or resistance to infection. The old paradigm of a susceptibility-associated Th1 versus a resistance-associated Th2-type response has been supplemented in recent years with cell populations such as novel innate lymphoid cells, basophils, dendritic cells and regulatory T cells proposed to play an active role in responses to T. muris infection. Moreover, new immune-controlled mechanisms of expulsion, such as increased epithelial cell turnover and mucin secretion, have been described in recent years increasing the number of possible targets for anti-parasite therapies. In this review, we give a comprehensive overview of experimental work conducted on the T. muris infection model, focusing on important findings and the most recent reports on the role of the immune system in parasite expulsion.

  11. Bessel collocation approach for approximate solutions of Hantavirus infection model

    Directory of Open Access Journals (Sweden)

    Suayip Yuzbasi

    2017-11-01

    Full Text Available In this study, a collocation method is introduced to find the approximate solutions of Hantavirus infection model which is a system of nonlinear ordinary differential equations. The method is based on the Bessel functions of the first kind, matrix operations and collocation points. This method converts Hantavirus infection model into a matrix equation in terms of the Bessel functions of first kind, matrix operations and collocation points. The matrix equation corresponds to a system of nonlinear equations with the unknown Bessel coefficients. The reliability and efficiency of the suggested scheme are demonstrated by numerical applications and all numerical calculations have been done by using a program written in Maple.

  12. Modeling Acinetobacter baumannii wound infections: The critical role of iron

    Science.gov (United States)

    Fleming, Irma D.; Krezalek, Monika A.; Belogortseva, Natalia; Zaborin, Alexander; Defazio, Jennifer; Chandrasekar, Laxmipradha; Actis, Luis A.; Zaborina, Olga; Alverdy, John C.

    2016-01-01

    Background Acinetobacter baumannii has emerged as an increasingly important and successful opportunistic human pathogen due to its ability to withstand harsh environmental conditions, its characteristic virulence factors and quick adaptability to stress. Methods We developed a clinically relevant murine model of A. baumannii traumatic wound infection to determine the effect of local wound environment on A. baumannii virulence. Mice underwent rectus muscle crush injury combined with ischemia created by epigastric vessel ligation, followed by A. baumannii inoculation. Reiterative experiments were performed using 1) a mutant deficient in the production of the siderophore acinetobactin, or 2) iron supplementation of the wound milieu. Mice were euthanized 7 days later and rectus muscle analyzed for signs of clinical infection, HIF1α accumulation, bacterial abundance and colony morphotype. To determine the effect of wound milieu on bacterial virulence, the Galleria mellonella infection model was utilized. Results The combination of rectus muscle injury with ischemia and A. baumannii inoculation resulted in 100% incidence of clinical wound infection that was significantly higher compared to other groups (n=15/group, pbaumannii colonization (pbaumannii strains isolated from injured/ischemic muscle with clinical infection displayed a rough morphotype and a higher degree of virulence as judged by G. mellonella killing assay as compared to smooth morphotype colonies isolated from injured muscle without clinical infection (100% vs. 60%, n=30 Log-Rank test, p=0.0422). Iron supplementation prevented wound infection (n=30, pbaumannii wild type was replaced with its derivative mutant ΔBasD deficient in acinetobactin production. Conclusions The ability of A. baumannii to cause infections in traumatized wound relies on its ability to scavenge iron and can be prevented by iron supplementation to the wound milieu. PMID:28030490

  13. Murine model for congenital CMV infection and hearing impairment

    Directory of Open Access Journals (Sweden)

    Tao Liu

    2011-02-01

    Full Text Available Abstract Background Congenital cytomegalovirus (CMV infection is the leading cause of sensorineural hearing loss (SNHL, and SNHL is the most frequent sequela of congenital CMV infection. But the pathogenic mechanism remains unknown, and there is no ideal CMV intrauterine infection animal model to study the mechanisms by which SNHL develops. Methods We established the congenital murine cytomegalovirus (MCMV infection model by directly injecting the virus into the placenta on day 12.5 of gestation. Then, we observed the development and the MCMV congenital infection rate of the fetuses on the day they were born. Furthermore, we detected the auditory functions, the conditions of the MCMV infection, and the histological change of the inner ears of 28-day-old and 70-day-old offspring. Results Both the fetal loss rate and the teratism rate of offspring whose placentas were inoculated with MCMV increased, and their body length, head circumference, and weight decreased. The hearing level of offspring both decreased at both 28- and 70-days post birth; the 70-day-old mice developed lower hearing levels than did the 28-day old mice. No significant inflammatory changes in the cochleae of the mice were observed. MCMV DNA signals were mainly detected in the spiral ganglion neurons and the endolymph area, but not in the perilymph area. The number of neurons decreased, and their ultrastructures changed. Moreover, with age, the number of neurons dramatically decreased, and the ultrastructural lesions of neurons became much more severe. Conclusions The results suggest that the direct injection of MCMV into the placenta may efficiently cause fetal infection and disturb the intrauterine development of the fetus, and placental inoculation itself has no obvious adverse effects on offspring. The reduction in the number of spiral ganglion neurons and the ultrastructural lesions of the neurons may be the major cause of congenital CMV infection-induced progressive SNHL.

  14. An Alternative Approach to Combination Vaccines: Intradermal Administration of Isolated Components for Control of Anthrax, Botulism, Plague and Staphylococcal Toxic Shock

    National Research Council Canada - National Science Library

    Morefield, Garry L; Tammariello, Ralph F; Purcell, Bret K; Worsham, Patricia L; Chapman, Jennifer; Smith, Leonard A; Alarcon, Jason B; Mikszta, John A; Ulrich, Robert G

    2008-01-01

    ... incompatible vaccine mixtures. Intradermally administered arrays of vaccines for protection from anthrax, botulism, plague, and staphylococcal toxic shock were biocompatible in vivo, retained potent antibody responses...

  15. A guinea pig model of Zika virus infection.

    Science.gov (United States)

    Kumar, Mukesh; Krause, Keeton K; Azouz, Francine; Nakano, Eileen; Nerurkar, Vivek R

    2017-04-11

    Animal models are critical to understand disease and to develop countermeasures for the ongoing epidemic of Zika virus (ZIKV). Here we report that immunocompetent guinea pigs are susceptible to infection by a contemporary American strain of ZIKV. Dunkin-Hartley guinea pigs were inoculated with 10 6 plaque-forming units of ZIKV via subcutaneous route and clinical signs were observed. Viremia, viral load in the tissues, anti-ZIKV neutralizing antibody titer, and protein levels of multiple cytokine and chemokines were analyzed using qRT-PCR, plaque assay, plaque reduction neutralization test (PRNT) and multiplex immunoassay. Upon subcutaneous inoculation with PRVABC59 strain of ZIKV, guinea pigs demonstrated clinical signs of infection characterized by fever, lethargy, hunched back, ruffled fur, and decrease in mobility. ZIKV was detected in the whole blood and serum using qRT-PCR and plaque assay. Anti-ZIKV neutralizing antibody was detected in the infected animals using PRNT. ZIKV infection resulted in a dramatic increase in protein levels of multiple cytokines, chemokines and growth factors in the serum. ZIKV replication was observed in spleen and brain, with the highest viral load in the brain. This data demonstrate that after subcutaneous inoculation, the contemporary ZIKV strain is neurotropic in guinea pigs. The guinea pig model described here recapitulates various clinical features and viral kinetics observed in ZIKV-infected patients, and therefore may serve as a model to study ZIKV pathogenesis, including pregnancy outcomes and for evaluation of vaccines and therapeutics.

  16. A micro-epidemic model for primary dengue infection

    Science.gov (United States)

    Mishra, Arti; Gakkhar, Sunita

    2017-06-01

    In this paper, a micro-epidemic non-linear dynamical model has been proposed and analyzed for primary dengue infection. The model incorporates the effects of T cells immune response as well as humoral response during pathogenesis of dengue infection. The time delay has been accounted for production of antibodies from B cells. The basic reproduction number (R0) has been computed. Three equilibrium states are obtained. The existence and stability conditions for infection-free and ineffective cellular immune response state have been discussed. The conditions for existence of endemic state have been obtained. Further, the parametric region is obtained where system exhibits complex behavior. The threshold value of time delay has been computed which is critical for change in stability of endemic state. A threshold level for antibodies production rate has been obtained over which the infection will die out even though R0 > 1. The model is in line with the clinical observation that viral load decreases within 7-14 days from the onset of primary infection.

  17. A Murine Model for Escherichia coli Urinary Tract Infection.

    Science.gov (United States)

    Hannan, Thomas J; Hunstad, David A

    2016-01-01

    Urinary tract infections (UTI) are among the most common bacterial infections of humans. The mouse provides an excellent and tractable model system for cystitis and pyelonephritis caused by Escherichia coli and other uropathogens. Using a well-established model of experimental cystitis in which the bladders of female mice are infected via transurethral catheterization, the molecular details of the pathogenesis of bacterial cystitis have been substantially illuminated in the last decade. Uropathogenic E. coli attach to bladder epithelium (both in human and mouse) via adhesive type 1 pili, establish a replicative niche within epithelial cell cytoplasm, and form intracellular bacterial communities that are protected from antibiotic effects and immune clearance. The use of different inbred and mutant mouse strains offers the opportunity to study outcomes of infection, including resolution, formation of quiescent intracellular bacterial reservoirs, chronic bacterial cystitis, and recurrent infections. Urine, bladder, and kidney tissues can be analyzed by bacterial culture, histology, immunohistochemistry, immunofluorescent and confocal microscopy, electron microscopy, and flow cytometry, while a broad array of soluble markers (e.g., cytokines) can also be profiled in serum, urine, and tissue homogenates by ELISA, Western blotting, multiplex bead array, and other approaches. This model promises to afford continued opportunity for discovery of pathogenic mechanisms and evaluation of therapeutic and preventive strategies for acute, chronic, and recurrent UTI.

  18. Modelling co-infection with malaria and lymphatic filariasis.

    Directory of Open Access Journals (Sweden)

    Hannah C Slater

    Full Text Available Malaria and lymphatic filariasis (LF continue to cause a considerable public health burden globally and are co-endemic in many regions of sub-Saharan Africa. These infections are transmitted by the same mosquito species which raises important questions about optimal vector control strategies in co-endemic regions, as well as the effect of the presence of each infection on endemicity of the other; there is currently little consensus on the latter. The need for comprehensive modelling studies to address such questions is therefore significant, yet very few have been undertaken to date despite the recognised explanatory power of reliable dynamic mathematical models. Here, we develop a malaria-LF co-infection modelling framework that accounts for two key interactions between these infections, namely the increase in vector mortality as LF mosquito prevalence increases and the antagonistic Th1/Th2 immune response that occurs in co-infected hosts. We consider the crucial interplay between these interactions on the resulting endemic prevalence when introducing each infection in regions where the other is already endemic (e.g. due to regional environmental change, and the associated timescale for such changes, as well as effects on the basic reproduction number R₀ of each disease. We also highlight potential perverse effects of vector controls on human infection prevalence in co-endemic regions, noting that understanding such effects is critical in designing optimal integrated control programmes. Hence, as well as highlighting where better data are required to more reliably address such questions, we provide an important framework that will form the basis of future scenario analysis tools used to plan and inform policy decisions on intervention measures in different transmission settings.

  19. Clostridium Difficile Infection Due to Pneumonia Treatment: Mortality Risk Models.

    Science.gov (United States)

    Chmielewska, M; Zycinska, K; Lenartowicz, B; Hadzik-Błaszczyk, M; Cieplak, M; Kur, Z; Wardyn, K A

    2017-01-01

    One of the most common gastrointestinal infection after the antibiotic treatment of community or nosocomial pneumonia is caused by the anaerobic spore Clostridium difficile (C. difficile). The aim of this study was to retrospectively assess mortality due to C. difficile infection (CDI) in patients treated for pneumonia. We identified 94 cases of post-pneumonia CDI out of the 217 patients with CDI. The mortality issue was addressed by creating a mortality risk models using logistic regression and multivariate fractional polynomial analysis. The patients' demographics, clinical features, and laboratory results were taken into consideration. To estimate the influence of the preceding respiratory infection, a pneumonia severity scale was included in the analysis. The analysis showed two statistically significant and clinically relevant mortality models. The model with the highest prognostic strength entailed age, leukocyte count, serum creatinine and urea concentration, hematocrit, coexisting neoplasia or chronic obstructive pulmonary disease. In conclusion, we report on two prognostic models, based on clinically relevant factors, which can be of help in predicting mortality risk in C. difficile infection, secondary to the antibiotic treatment of pneumonia. These models could be useful in preventive tailoring of individual therapy.

  20. Non-Human Primate Models of Orthopoxvirus Infections

    Directory of Open Access Journals (Sweden)

    Anne Schmitt

    2014-06-01

    Full Text Available Smallpox, one of the most destructive diseases, has been successfully eradicated through a worldwide vaccination campaign. Since immunization programs have been stopped, the number of people with vaccinia virus induced immunity is declining. This leads to an increase in orthopoxvirus (OPXV infections in humans, as well as in animals. Additionally, potential abuse of Variola virus (VARV, the causative agent of smallpox, or monkeypox virus, as agents of bioterrorism, has renewed interest in development of antiviral therapeutics and of safer vaccines. Due to its high risk potential, research with VARV is restricted to two laboratories worldwide. Therefore, numerous animal models of other OPXV infections have been developed in the last decades. Non-human primates are especially suitable due to their close relationship to humans. This article provides a review about on non-human primate models of orthopoxvirus infections.

  1. Animal Models of Zika Virus Infection, Pathogenesis, and Immunity.

    Science.gov (United States)

    Morrison, Thomas E; Diamond, Michael S

    2017-04-15

    Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis. Copyright © 2017 American Society for Microbiology.

  2. Influence of glucocorticoids on a time-of-day-dependent variation in intradermal reactivity to histamine in dogs.

    Science.gov (United States)

    Goto, Shun; Shimizu, Sunao; Watanabe, Miwa; Osada, Hironari; Sasaki, Kazuaki; Shimoda, Minoru; Nagai, Makoto; Shirai, Junsuke; Itoh, Hiroshi; Ohmori, Keitaro

    2016-08-01

    The objectives of this study were to determine daily variation in intradermal reactivity to histamine in dogs and to evaluate a potential influence of glucocorticoids on reactivity. Wheal sizes formed after intradermal injections of histamine were measured every 6 h during a single 24 h period in six healthy dogs. To determine whether glucocorticoids were implicated in daily variation, intradermal reactivity to histamine was evaluated at 9:00 h and at 21:00 h during a single day in dogs that received oral prednisolone (a synthetic glucocorticoid) or oral trilostane (an inhibitor of endogenous glucocorticoid synthesis). Finally, the time required for the histamine reaction to diminish after an intravenous injection of hydrocortisone was also assessed. A significant time-of-day-dependent variation in intradermal reactivity to histamine was detected in dogs, with a larger wheal size observed at 9:00 h than at 21:00 h. Administration of prednisolone or trilostane disrupted this variation. Intradermal reactivity to histamine was significantly reduced 6 h after an intravenous injection of hydrocortisone. These results suggest that glucocorticoid secretion from the adrenal glands could be involved in the regulation of daily variation in histamine-mediated reactions in dogs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Safety, tolerability and efficacy of intradermal rabies immunization with DebioJect™.

    Science.gov (United States)

    Vescovo, Paul; Rettby, Nils; Ramaniraka, Nirinarilala; Liberman, Julie; Hart, Karen; Cachemaille, Astrid; Piveteau, Laurent-Dominique; Zanoni, Reto; Bart, Pierre-Alexandre; Pantaleo, Giuseppe

    2017-03-27

    In a single-center study, 66 healthy volunteers aged between 18 and 50years were randomized to be immunized against rabies with three different injection routes: intradermal with DebioJect™ (IDJ), standard intradermal with classical needle (IDS), also called Mantoux method, and intramuscular with classical needle (IM). "Vaccin rabique Pasteur®" and saline solution (NaCl 0.9%) were administered at D0, D7 and D28. Antigen doses for both intradermal routes were 1/5 of the dose for IM. Tolerability, safety and induced immunogenicity of IDJ were compared to IDS and IM routes. Pain was evaluated at needle insertion and at product injection for all vaccination visits. Solicited Adverse Event (SolAE) and local reactogenicity symptoms including pain, redness and pruritus were recorded daily following each vaccination visit. Adverse events (AE) were recorded over the whole duration of the study. Humoral immune response was measured by assessing the rabies virus neutralizing antibody (VNA) titers using Rapid Fluorescent Focus Inhibition Test (RFFIT). Results demonstrated that the DebioJect™ is a safe, reliable and efficient device. Significant decreases of pain at needle insertion and at vaccine injection were reported with IDJ compared to IDS and IM. All local reactogenicity symptoms (pain, redness and pruritus) after injection with either vaccine or saline solution, were similar for IDJ and IDS, except that IDJ injection induced more redness 30min after saline solution. No systemic SolAE was deemed related to DebioJect™ and classical needles. No AE was deemed related to DebioJect™. No Serious Adverse Event (SAE) was reported during the study. At the end of the study all participants were considered immunized against rabies and no significant difference in humoral response was observed between the 3 studied routes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Systemic and local immune response in pigs intradermally and intramuscularly injected with inactivated Mycoplasma hyopneumoniae vaccines.

    Science.gov (United States)

    Martelli, P; Saleri, R; Cavalli, V; De Angelis, E; Ferrari, L; Benetti, M; Ferrarini, G; Merialdi, G; Borghetti, P

    2014-01-31

    The systemic and respiratory local immune response induced by the intradermal administration of a commercial inactivated Mycoplasma hyopneumoniae whole-cell vaccine (Porcilis(®) MHYO ID ONCE - MSD AH) in comparison with two commercial vaccines administered via the intramuscular route and a negative control (adjuvant only) was investigated. Forty conventional M. hyopneumoniae-free pigs were randomly assigned to four groups (ten animals each): Group A=intradermal administration of the test vaccine by using the needle-less IDAL(®) vaccinator at a dose of 0.2 ml; Group B=intramuscular administration of a commercially available vaccine (vaccine B); Group C=intramuscular administration of the adjuvant only (2 ml of X-solve adjuvant); Group D=intramuscular administration of a commercially available vaccine (vaccine D). Pigs were vaccinated at 28 days of age. Blood and bronchoalveolar lavage (BAL) fluid samples were collected at vaccination (blood only), 4 and 8 weeks post-vaccination. Serum and BAL fluid were tested for the presence of antibodies by ELISA test. Peripheral blood monomorphonuclear cells (PBMC) were isolated to quantify the number of IFN-γ secreting cells by ELISpot. Moreover, cytokine gene expression from the BAL fluid was performed. Total antibodies against M. hyopneumoniae and specific IgG were detected in serum of intradermally and intramuscularly (vaccine B only) vaccinated pigs at 4 and 8 weeks post-vaccination. M. hyopneumoniae specific IgA were detected in BAL fluid from vaccinated animals (Groups A and B) but not from controls and animals vaccinated with the bacterin D (padministration of an adjuvanted bacterin induces both systemic and mucosal immune responses. Moreover, the intramuscularly administered commercial vaccines each had a different ability to stimulate the immune response both systemically and locally. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. ZnO Nano-Rod Devices for Intradermal Delivery and Immunization.

    Science.gov (United States)

    Nayak, Tapas R; Wang, Hao; Pant, Aakansha; Zheng, Minrui; Junginger, Hans; Goh, Wei Jiang; Lee, Choon Keong; Zou, Shui; Alonso, Sylvie; Czarny, Bertrand; Storm, Gert; Sow, Chorng Haur; Lee, Chengkuo; Pastorin, Giorgia

    2017-06-15

    Intradermal delivery of antigens for vaccination is a very attractive approach since the skin provides a rich network of antigen presenting cells, which aid in stimulating an immune response. Numerous intradermal techniques have been developed to enhance penetration across the skin. However, these methods are invasive and/or affect the skin integrity. Hence, our group has devised zinc oxide (ZnO) nano-rods for non-destructive drug delivery. Chemical vapour deposition was used to fabricate aligned nano-rods on ZnO pre-coated silicon chips. The nano-rods' length and diameter were found to depend on the temperature, time, quality of sputtered silicon chips, etc. Vertically aligned ZnO nano-rods with lengths of 30-35 µm and diameters of 200-300 nm were selected for in vitro human skin permeation studies using Franz cells with Albumin-fluorescein isothiocyanate (FITC) absorbed on the nano-rods. Fluorescence and confocal studies on the skin samples showed FITC penetration through the skin along the channels formed by the nano-rods. Bradford protein assay on the collected fluid samples indicated a significant quantity of Albumin-FITC in the first 12 h. Low antibody titres were observed with immunisation on Balb/c mice with ovalbumin (OVA) antigen coated on the nano-rod chips. Nonetheless, due to the reduced dimensions of the nano-rods, our device offers the additional advantage of excluding the simultaneous entrance of microbial pathogens. Taken together, these results showed that ZnO nano-rods hold the potential for a safe, non-invasive, and painless intradermal drug delivery.

  6. Takeover times for a simple model of network infection

    Science.gov (United States)

    Ottino-Löffler, Bertrand; Scott, Jacob G.; Strogatz, Steven H.

    2017-07-01

    We study a stochastic model of infection spreading on a network. At each time step a node is chosen at random, along with one of its neighbors. If the node is infected and the neighbor is susceptible, the neighbor becomes infected. How many time steps T does it take to completely infect a network of N nodes, starting from a single infected node? An analogy to the classic "coupon collector" problem of probability theory reveals that the takeover time T is dominated by extremal behavior, either when there are only a few infected nodes near the start of the process or a few susceptible nodes near the end. We show that for N ≫1 , the takeover time T is distributed as a Gumbel distribution for the star graph, as the convolution of two Gumbel distributions for a complete graph and an Erdős-Rényi random graph, as a normal for a one-dimensional ring and a two-dimensional lattice, and as a family of intermediate skewed distributions for d -dimensional lattices with d ≥3 (these distributions approach the convolution of two Gumbel distributions as d approaches infinity). Connections to evolutionary dynamics, cancer, incubation periods of infectious diseases, first-passage percolation, and other spreading phenomena in biology and physics are discussed.

  7. Animal Model Reveals Potential Waterborne Transmission of Helicobacter pylori Infection.

    Science.gov (United States)

    Boehnke, Kevin F; Eaton, Kathryn A; Valdivieso, Manuel; Baker, Laurence H; Xi, Chuanwu

    2015-10-01

    Helicobacter pylori infection has been consistently associated with lack of access to clean water and proper sanitation, but no studies have demonstrated that the transmission of H. pylori can occur from drinking contaminated water. In this study, we used a laboratory mouse model to test whether waterborne H. pylori could cause gastric infection. Groups of immunocompetent C57/BL6 Helicobacter-free mice were exposed to static concentrations (1.29 × 10(5), 10(6), 10(7), 10(8), and 10(9) CFU/L) of H. pylori in their drinking water for 4 weeks. One group of Helicobacter-free mice was exposed to uncontaminated water as a negative control. H. pylori morphology changes in water were examined using microscopy Live/Dead staining. Following exposure, H. pylori infection and inflammation status in the stomach were evaluated using quantitative culture, PCR, the rapid urease test, and histology. None of the mice in the negative control or 10(5) groups were infected. One of 20 cages (one of 40 mice) of the 10(6) group, three of 19 cages (four of 38 mice) of the 10(7) CFU/L group, 19 of 20 cages (33 of 40 mice) of the 10(8) group, and 20 of 20 cages (39 of 40 mice) of the 10(9) CFU/L group were infected. Infected mice had significantly higher gastric inflammation than uninfected mice (27.86% higher inflammation, p pylori in water is infectious in mice, suggesting that humans drinking contaminated water may be at risk of contracting H. pylori infection. Much work needs to be performed to better understand the risk of infection from drinking H. pylori-contaminated water. © 2015 John Wiley & Sons Ltd.

  8. Reproducible Infection Model for Clostridium perfringens in Broiler Chickens

    DEFF Research Database (Denmark)

    Pedersen, Karl; Friis-Holm, Lotte Bjerrum; Heuer, Ole Eske

    2008-01-01

    Experiments were carried out to establish an infection and disease model for Clostridium perfringens in broiler chickens. Previous experiments had failed to induce disease and only a transient colonization with challenge strains had been obtained. In the present study, two series of experiments...

  9. Modeling dynamics of HIV infected cells using stochastic cellular automaton

    Science.gov (United States)

    Precharattana, Monamorn; Triampo, Wannapong

    2014-08-01

    Ever since HIV was first diagnosed in human, a great number of scientific works have been undertaken to explore the biological mechanisms involved in the infection and progression of the disease. Several cellular automata (CA) models have been introduced to gain insights into the dynamics of the disease progression but none of them has taken into account effects of certain immune cells such as the dendritic cells (DCs) and the CD8+ T lymphocytes (CD8+ T cells). In this work, we present a CA model, which incorporates effects of the HIV specific immune response focusing on the cell-mediated immunities, and investigate the interaction between the host immune response and the HIV infected cells in the lymph nodes. The aim of our work is to propose a model more realistic than the one in Precharattana et al. (2010) [10], by incorporating roles of the DCs, the CD4+ T cells, and the CD8+ T cells into the model so that it would reproduce the HIV infection dynamics during the primary phase of HIV infection.

  10. Should the General Practitioner Consider Mesotherapy (Intradermal Therapy) to Manage Localized Pain?

    Science.gov (United States)

    Mammucari, Massimo; Maggiori, Enrica; Lazzari, Marzia; Natoli, Silvia

    2016-06-01

    Wide variations in the types of pain and response to analgesic pharmacotherapy mean that a variety of treatment strategies are needed. One approach is mesotherapy (intradermal therapy). This consists of microinjections into the skin and is ideally suited to the management of localized pain. Advantages include increasing the duration of drug activity, reduced risk of adverse events and interactions, and possible synergy with other therapies. Mesotherapy provides general practitioners with another tool for the treatment of local pain. However, it is important to provide patients with full details of the pros and cons of this approach and obtain informed patient consent.

  11. The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections.

    Science.gov (United States)

    Tängdén, T; Ramos Martín, V; Felton, T W; Nielsen, E I; Marchand, S; Brüggemann, R J; Bulitta, J B; Bassetti, M; Theuretzbacher, U; Tsuji, B T; Wareham, D W; Friberg, L E; De Waele, J J; Tam, V H; Roberts, Jason A

    2017-07-01

    Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed. Use of such regimens often results in inadequate antimicrobial concentrations at the site of infection and is associated with poor patient outcomes. In this article, we describe the potential of in vitro and in vivo infection models, clinical pharmacokinetic data and pharmacokinetic/pharmacodynamic models to guide the design of more effective antimicrobial dosing regimens. Individualised dosing, based on population PK models and patient factors (e.g. renal function and weight) known to influence antimicrobial PK, increases the probability of achieving therapeutic drug exposures while at the same time avoiding toxic concentrations. When therapeutic drug monitoring (TDM) is applied, early dose adaptation to the needs of the individual patient is possible. TDM is likely to be of particular importance for infected critically ill patients, where profound PK changes are present and prompt appropriate antibiotic therapy is crucial. In the light of the continued high mortality rates in critically ill patients with severe infections, a paradigm shift to refined dosing strategies for antimicrobials is warranted to enhance the probability of achieving drug concentrations that increase the likelihood of clinical success.

  12. Choosing an Appropriate Infection Model to Study Quorum Sensing Inhibition in Pseudomonas Infections

    Directory of Open Access Journals (Sweden)

    Evelina Papaioannou

    2013-09-01

    Full Text Available Bacteria, although considered for decades to be antisocial organisms whose sole purpose is to find nutrients and multiply are, in fact, highly communicative organisms. Referred to as quorum sensing, cell-to-cell communication mechanisms have been adopted by bacteria in order to co-ordinate their gene expression. By behaving as a community rather than as individuals, bacteria can simultaneously switch on their virulence factor production and establish successful infections in eukaryotes. Understanding pathogen-host interactions requires the use of infection models. As the use of rodents is limited, for ethical considerations and the high costs associated with their use, alternative models based on invertebrates have been developed. Invertebrate models have the benefits of low handling costs, limited space requirements and rapid generation of results. This review presents examples of such models available for studying the pathogenicity of the Gram-negative bacterium Pseudomonas aeruginosa. Quorum sensing interference, known as quorum quenching, suggests a promising disease-control strategy since quorum-quenching mechanisms appear to play important roles in microbe-microbe and host-pathogen interactions. Examples of natural and synthetic quorum sensing inhibitors and their potential as antimicrobials in Pseudomonas-related infections are discussed in the second part of this review.

  13. Mouse models of dengue virus infection for vaccine testing.

    Science.gov (United States)

    Sarathy, Vanessa V; Milligan, Gregg N; Bourne, Nigel; Barrett, Alan D T

    2015-12-10

    Dengue is a mosquito-borne disease caused by four serologically and genetically related viruses termed DENV-1 to DENV-4. With an annual global burden of approximately 390 million infections occurring in the tropics and subtropics worldwide, an effective vaccine to combat dengue is urgently needed. Historically, a major impediment to dengue research has been development of a suitable small animal infection model that mimics the features of human illness in the absence of neurologic disease that was the hallmark of earlier mouse models. Recent advances in immunocompromised murine infection models have resulted in development of lethal DENV-2, DENV-3 and DENV-4 models in AG129 mice that are deficient in both the interferon-α/β receptor (IFN-α/β R) and the interferon-γ receptor (IFN-γR). These models mimic many hallmark features of dengue disease in humans, such as viremia, thrombocytopenia, vascular leakage, and cytokine storm. Importantly AG129 mice develop lethal, acute, disseminated infection with systemic viral loads, which is characteristic of typical dengue illness. Infected AG129 mice generate an antibody response to DENV, and antibody-dependent enhancement (ADE) models have been established by both passive and maternal transfer of DENV-immune sera. Several steps have been taken to refine DENV mouse models. Viruses generated by peripheral in vivo passages incur substitutions that provide a virulent phenotype using smaller inocula. Because IFN signaling has a major role in immunity to DENV, mice that generate a cellular immune response are desired, but striking the balance between susceptibility to DENV and intact immunity is complicated. Great strides have been made using single-deficient IFN-α/βR mice for DENV-2 infection, and conditional knockdowns may offer additional approaches to provide a panoramic view that includes viral virulence and host immunity. Ultimately, the DENV AG129 mouse models result in reproducible lethality and offer multiple

  14. Analyses of homologous rotavirus infection in the mouse model.

    Science.gov (United States)

    Burns, J W; Krishnaney, A A; Vo, P T; Rouse, R V; Anderson, L J; Greenberg, H B

    1995-02-20

    The group A rotaviruses are significant human and veterinary pathogens in terms of morbidity, mortality, and economic loss. Despite its importance, an effective vaccine remains elusive due at least in part to our incomplete understanding of rotavirus immunity and protection. Both large and small animal model systems have been established to address these issues. One significant drawback of these models is the lack of well-characterized wild-type homologous viruses and their cell culture-adapted variants. We have characterized four strains of murine rotaviruses, EC, EHP, EL, and EW, in the infant and adult mouse model using wild-type isolates and cell culture-adapted variants of each strain. Wild-type murine rotaviruses appear to be equally infectious in infant and adult mice in terms of the intensity and duration of virus shedding following primary infection. Spread of infection to naive cagemates is seen in both age groups. Clearance of shedding following primary infection appears to correlate with the development of virus-specific intestinal IgA. Protective immunity is developed in both infant and adult mice following oral infection as demonstrated by a lack of shedding after subsequent wild-type virus challenge. Cell culture-adapted murine rotaviruses appear to be highly attenuated when administered to naive animals and do not spread efficiently to nonimmune cagemates. The availability of these wild-type and cell culture-adapted virus preparations should allow a more systematic evaluation of rotavirus infection and immunity. Furthermore, future vaccine strategies can be evaluated in the mouse model using several fully virulent homologous viruses for challenge.

  15. Porcine models of biofilm infections with focus on pathomorphology

    DEFF Research Database (Denmark)

    Jensen, Louise Kruse; Johansen, Anne Sofie Boyum; Jensen, Henrik Elvang

    2017-01-01

    Bacterial biofilm formation is one of the main reasons for a negative treatment outcome and a high recurrence rate for many chronic infections in humans. The optimal way to study both the biofilm forming bacteria and the host response simultaneously is by using discriminative, reliable, and repro......Bacterial biofilm formation is one of the main reasons for a negative treatment outcome and a high recurrence rate for many chronic infections in humans. The optimal way to study both the biofilm forming bacteria and the host response simultaneously is by using discriminative, reliable......, physiology, and immune system to humans. Furthermore, conventional pigs spontaneously develop many of the same chronic bacterial infections as seen in humans. Therefore, in this review porcine models of five different infectious diseases all associated with biofilm formation and chronicity in humans...... are described. The infectious diseases are: chronic wounds, endocarditis, pyelonephritis, hematogenous osteomyelitis, and implant-associated osteomyelitis (IAO)....

  16. The comparative performance of the single intradermal comparative tuberculin test in Irish cattle, using tuberculin PPD combinations from different manufacturers.

    Science.gov (United States)

    Good, M; Clegg, T A; Murphy, F; More, S J

    2011-07-05

    Ireland currently obtains its avian and bovine tuberculin purified protein derivatives (PPDs) from a single source. Because problems of supply or quality cannot be discounted, it is prudent that Ireland identify alternative supplier(s) as part of a broad risk management strategy. Therefore, the aim of this study was to compare the performance of a number of different tuberculin combinations (that is, pairings of bovine and avian PPD; with different manufacturers) in the single intradermal comparative tuberculin test (SICTT), as currently performed in Ireland. The study was randomised, controlled and double-blinded. A total of 2172 cattle were used in the study. Each animal was tested using two SICTTs, the first based on the tuberculin combination in current use, and the second using one of six trial tuberculin combinations. Analyses were conducted to compare both reactor-status and skin increase. For each control/trial tuberculin combination, there was good agreement between the control and trial reactor-status. Differences in skin increases were mainly confined to animals categorised as either negative or severe inconclusive. However, the measured differences were minor, and unlikely to have a significant impact on the actual test outcome, either for individual animals or for herds. In conclusion, while further studies determining sensitivity and specificity in Ireland would have to be done in the event of a change in tuberculin PPD there should be minimal disruption of the national programme if alternative tuberculin PPDs meeting WHO, OIE and EU regulations were used. In this study, the precision of the guinea pig bio-assay to assess tuberculin potency was low and therefore Ireland should maintain its practice of periodically assessing potency in naturally infected cattle, even though this is not currently required under WHO, OIE or EU Regulations. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Intradermal Infiltration of Local Anesthetic-Rapid and Bloodless Deepithelialization of the Breast Pedicle.

    Science.gov (United States)

    Bennett, Katelyn G; Gilman, Robert H

    2017-02-01

    Breast reduction is one of the most commonly performed plastic surgery procedures, and pedicle deepithelialization remains a time-consuming step of the operation. This is especially true when using an inferior pedicle. We present a novel technique of intradermal infiltration of the breast pedicle with local anesthetic to facilitate efficient, bloodless deepithelialization. The senior author uses a 20-ml syringe to inject 0.25% lidocaine and 1:400,000 epinephrine just beneath the epidermis of the breast pedicle to create a series of wheals. Approximately 20 ml of local anesthetic is used per pedicle. After injection of local anesthetic, the breast pedicle is deepithelialized in less than 3 minutes. The plane is bloodless, allowing improved visualization secondary to the epinephrine-induced hemostasis. The senior author has had only one case of nipple necrosis in 20 years of experience. Intradermal infiltration of local anesthetic with epinephrine hydrodissects between the epidermis and dermis and provides hemostasis to facilitate rapid deepithelialization.

  18. Effect analysis of intradermal hyaluronic acid injection to treat enlarged facial pores.

    Science.gov (United States)

    Qian, Wei; Zhang, Yan-Kun; Hou, Ying; Lyu, Wei; Cao, Qian; Li, Yan-Qi; Fan, Ju-Feng

    2017-08-08

    To investigate the clinical application and efficacy of intradermal injection of low molecular weight hyaluronic acid (LMW-HA) for treating enlarged facial pores. From January 2015 to May 2016, 42 subjects who sought aesthetic treatment underwent intradermal injection of LMW-HA to improve enlarged facial pores. For each treatment, 2.5 mL (25 mg) of LMW-HA was injected into the skin of the full face. The treatment was repeated 2-5 times with an interval of 1 to 1.5 months between consecutive treatments. The postoperative follow-up period was 1 to 6 months. Statistical analysis was used to compare the degree of enlargement of facial pores before and after injection. The clinical efficacy and adverse effects were recorded. The enlarged facial pores before and after treatment were categorized and subjected to the Wilcoxon matched-pairs signed-rank test. The difference was statistically significant (Ppore size, and enhance skin radiance. The injection technique was simple, safe, and effective and could easily be extended to clinical practice. © 2017 Wiley Periodicals, Inc.

  19. Increased Sensitization to Mold Allergens Measured by Intradermal Skin Testing following Hurricanes

    Science.gov (United States)

    Hurst, David

    2017-01-01

    Objective. To report on changes in sensitivity to mold allergens determined by changes in intradermal skin testing reactivity, after exposure to two severe hurricanes. Methods. A random, retrospective allergy charts review divided into 2 groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior to hurricanes, and Group B, patients tested in 2014 and 2015 following hurricanes. Reactivity to eighteen molds was determined by intradermal skin testing. Test results, age, and respiratory symptoms were recorded. Chi-square test determined reactivity/sensitivity differences between groups. Results. Posthurricane patients had 34.6 times more positive results (p < 0.0001) at weaker dilutions, all tested molds were found to be more reactive, and 95% had at least one positive test versus only 62% before the hurricanes (p < 0.0001); average mold reactivity was 55% versus 16% while 17% of patients reacted to the entire panel versus none before the hurricanes (p < 0.0001). The posthurricane population was younger (p < 0.001) and included more patients with asthma or lower respiratory symptoms (p < 0.05). Conclusion. Reactivity and sensitization to mold allergens increased compared to patients before the hurricanes. This supports climatologists' hypothesis that environmental changes resulting from hurricanes can be a health risk as reflected in increased allergic sensitivities and symptoms and has significant implications for physicians treating patients from affected areas. PMID:28491100

  20. Cosmetic outcomes of cesarean section scar; subcuticular suture versus intradermal buried suture.

    Science.gov (United States)

    Yang, Juseok; Kim, Ki Hyung; Song, Yong Jung; Kim, Seung-Chul; Sung, Nayoung; Kim, Haneul; Lee, Dong Hyung

    2018-01-01

    The objective of the study was to compare cosmetic outcomes and overall satisfaction rate of cesarean section scar between conventional subcuticular suture and intradermal buried vertical mattress. Patients were enrolled to the study by chart review. A scar assessment was obtained retrospectively through a telephone survey. The patient component of the patient and observer scar assessment scale (POSAS) was utilized along with the overall satisfaction of the patient regarding their cesarean section scar and their willingness to choose the same skin closure technique when anticipating their next cesarean section. A total of 303 cases of cesarean section was recruited, 102 finished telephone surveys were calculated for the analyses. Subcuticular suture was regarded as control group (n=52) and intradermal buried suture as test group (n=50). The PSAS score of the test group (mean, 21.8) was lower than that of the control group (mean, 28), with a statistical significance ( P =0.02). Overall satisfaction rate did not differ between the two groups. Two parameters of the PSAS score and the level of overall satisfaction showed significant correlation (Pearson's r , -0.63; P cesarean sections over subcuticular stitch.

  1. Sequential treatment with intradermal incision (intracision) and 2,940-nm Er:YAG laser for chicken pox scars.

    Science.gov (United States)

    Lee, Sang Ju; Kim, Young Koo; Choi, Sun Young; Park, Kui Young; Seo, Seong Jun

    2014-01-01

    Boxcar scars, such as chicken pox scars, are round to oval depressions with sharply defined vertical edges. Subcision is a simple and safe procedure for treatment of atrophic and depressed scars, but boxcar scars are generally not eliminated by subcision. Intradermal incision technique (intracision) can treat chicken pox scars by untethering fibrotic strands, raising collagen synthesis, and having additional intradermal blood pocket formation. We have found that chicken pox scars further improve when intracision is followed by laser skin resurfacing. © 2013 Wiley Periodicals, Inc.

  2. Hendra and Nipah Infection: Pathology, Models and Potential Therapies

    Science.gov (United States)

    Vigant, Frederic; Lee, Benhur

    2011-01-01

    The Paramyxoviridae family comprises of several genera that contain emerging or re-emerging threats for human and animal health with no real specific effective treatment available. Hendra and Nipah virus are members of a newly identified genus of emerging paramyxoviruses, Henipavirus. Since their discovery in the 1990s, henipaviruses outbreaks have been associated with high economic and public health threat potential. When compared to other paramyxoviruses, henipaviruses appear to have unique characteristics. Henipaviruses are zoonotic paramyxoviruses with a broader tropism than most other paramyxoviruses, and can cause severe acute encephalitis with unique features among viral encephalitides. There are currently no approved effective prophylactic or therapeutic treatments for henipavirus infections. Although ribavirin was empirically used and seemed beneficial during the biggest outbreak caused by one of these viruses, the Nipah virus, its efficacy is disputed in light of its lack of efficacy in several animal models of henipavirus infection. Nevertheless, because of its highly pathogenic nature, much effort has been spent in developing anti-henipavirus therapeutics. In this review we describe the unique features of henipavirus infections and the different strategies and animal models that have been developed so far in order to identify and test potential drugs to prevent or treat henipavirus infections. Some of these components have the potential to be broad-spectrum antivirals as they target effectors of viral pathogenecity common to other viruses. We will focus on small molecules or biologics, rather than vaccine strategies, that have been developed as anti-henipaviral therapeutics. PMID:21488828

  3. Dynamics of a stochastic HIV-1 infection model with logistic growth

    Science.gov (United States)

    Jiang, Daqing; Liu, Qun; Shi, Ningzhong; Hayat, Tasawar; Alsaedi, Ahmed; Xia, Peiyan

    2017-03-01

    This paper is concerned with a stochastic HIV-1 infection model with logistic growth. Firstly, by constructing suitable stochastic Lyapunov functions, we establish sufficient conditions for the existence of ergodic stationary distribution of the solution to the HIV-1 infection model. Then we obtain sufficient conditions for extinction of the infection. The stationary distribution shows that the infection can become persistent in vivo.

  4. Mouse model for acute Epstein-Barr virus infection.

    Science.gov (United States)

    Wirtz, Tristan; Weber, Timm; Kracker, Sven; Sommermann, Thomas; Rajewsky, Klaus; Yasuda, Tomoharu

    2016-11-29

    Epstein-Barr Virus (EBV) infects human B cells and drives them into continuous proliferation. Two key viral factors in this process are the latent membrane proteins LMP1 and LMP2A, which mimic constitutively activated CD40 receptor and B-cell receptor signaling, respectively. EBV-infected B cells elicit a powerful T-cell response that clears the infected B cells and leads to life-long immunity. Insufficient immune surveillance of EBV-infected B cells causes life-threatening lymphoproliferative disorders, including mostly germinal center (GC)-derived B-cell lymphomas. We have modeled acute EBV infection of naive and GC B cells in mice through timed expression of LMP1 and LMP2A. Although lethal when induced in all B cells, induction of LMP1 and LMP2A in just a small fraction of naive B cells initiated a phase of rapid B-cell expansion followed by a proliferative T-cell response, clearing the LMP-expressing B cells. Interfering with T-cell activity prevented clearance of LMP-expressing B cells. This was also true for perforin deficiency, which in the human causes a life-threatening EBV-related immunoproliferative syndrome. LMP expression in GC B cells impeded the GC reaction but, upon loss of T-cell surveillance, led to fatal B-cell expansion. Thus, timed expression of LMP1 together with LMP2A in subsets of mouse B cells allows one to study major clinically relevant features of human EBV infection in vivo, opening the way to new therapeutic approaches.

  5. Treatment model of dengue hemorrhagic fever infection in human body

    Science.gov (United States)

    Handayani, D.; Nuraini, N.; Primasari, N.; Wijaya, K. P.

    2014-03-01

    The treatment model of DHF presented in this paper involves the dynamic of five time-dependent compartments, i.e. susceptible, infected, free virus particle, immune cell, and haematocrit level. The treatment model is investigated based on normalization of haematocrit level, which is expressed as intravenous fluid infusion control. We analyze the stability of the disease free equilibrium and the endemic equilibrium. The numerical simulations will explain the dynamic of each compartment in human body. These results show particularly that infected compartment and free virus particle compartment are tend to be vanished in two weeks after the onset of dengue virus. However, these simulation results also show that without the treatment, the haematocrit level will decrease even though not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control.

  6. Modeling environmental transmission of MAP infection in dairy cows.

    Science.gov (United States)

    De Silva, Kokum R; Eda, Shigetoshi; Lenhart, Suzanne

    2017-08-01

    Johne's disease is caused by Mycobacterium avium subspecies paratuberculosis(MAP). It is a chronic, progressive, and inflammatory disease which has a long incubation period. One main problem with the disease is the reduction of milk production in infected dairy cows. In our study we develop a system of ordinary differential equations to describe the dynamics of MAP infection in a dairy farm. This model includes the progression of the disease and the age structure of the cows. To investigate the effect of persistence of this bacteria on the farm on transmission in our model, we include environmental compartments, representing the pathogen input in an explicit way. The effect of indirect transmission from the bacteria in the environment and the culling of high-shedding adults can be seen in the numerical simulations. Since culling usually only happens once a year, we include a novel feature in the simulations with a discrete action of removing high-shedding adults once a year. We conclude that with culling of high shedders even at a high rate, the infection will persist in the modeled farm setting.

  7. A Susceptible Mouse Model for Zika Virus Infection.

    Directory of Open Access Journals (Sweden)

    Stuart D Dowall

    2016-05-01

    Full Text Available Zika virus (ZIKV is a mosquito-borne pathogen which has recently spread beyond Africa and into Pacific and South American regions. Despite first being detected in 1947, very little information is known about the virus, and its spread has been associated with increases in Guillain-Barre syndrome and microcephaly. There are currently no known vaccines or antivirals against ZIKV infection. Progress in assessing interventions will require the development of animal models to test efficacies; however, there are only limited reports on in vivo studies. The only susceptible murine models have involved intracerebral inoculations or juvenile animals, which do not replicate natural infection. Our report has studied the effect of ZIKV infection in type-I interferon receptor deficient (A129 mice and the parent strain (129Sv/Ev after subcutaneous challenge in the lower leg to mimic a mosquito bite. A129 mice developed severe symptoms with widespread viral RNA detection in the blood, brain, spleen, liver and ovaries. Histological changes were also striking in these animals. 129Sv/Ev mice developed no clinical symptoms or histological changes, despite viral RNA being detectable in the blood, spleen and ovaries, albeit at lower levels than those seen in A129 mice. Our results identify A129 mice as being highly susceptible to ZIKV and thus A129 mice represent a suitable, and urgently required, small animal model for the testing of vaccines and antivirals.

  8. Protection from lethal infection is determined by innate immune responses in a mouse model of Ebola virus infection

    International Nuclear Information System (INIS)

    Mahanty, Siddhartha; Gupta, Manisha; Paragas, Jason; Bray, Mike; Ahmed, Rafi; Rollin, Pierre E.

    2003-01-01

    A mouse-adapted strain of Ebola Zaire virus produces a fatal infection when BALB/cj mice are infected intraperitoneally (ip) but subcutaneous (sc) infection with the same virus fails to produce illness and confers long-term protection from lethal ip rechallenge. To identify immune correlates of protection in this model, we compared viral replication and cytokine/chemokine responses to Ebola virus in mice infected ip (10 PFU/mouse), or sc (100 PFU/mouse) and sc 'immune' mice rechallenged ip (10 6 PFU/mouse) at several time points postinfection (pi). Ebola viral antigens were detected in the serum, liver, spleen, and kidneys of ip-infected mice by day 2 pi, increasing up to day 6. Sc-infected mice and immune mice rechallenged ip had no detectable viral antigens until day 6 pi, when low levels of viral antigens were detected in the livers of sc-infected mice only. TNF-α and MCP-1 were detected earlier and at significantly higher levels in the serum and tissues of ip-infected mice than in sc-infected or immune mice challenged ip. In contrast, high levels of IFN-α and IFN-γ were found in tissues within 2 days after challenge in sc-infected and immune mice but not in ip-infected mice. Mice became resistant to ip challenge within 48 h of sc infection, coinciding with the rise in tissue IFN-α levels. In this model of Ebola virus infection, the nonlethal sc route of infection is associated with an attenuated inflammatory response and early production of antiviral cytokines, particularly IFN-α, as compared with lethal ip infection

  9. Virosomal hepatitis a vaccine: comparing intradermal and subcutaneous with intramuscular administration.

    Science.gov (United States)

    Frösner, Gert; Steffen, Robert; Herzog, Christian

    2009-01-01

    Vaccination against hepatitis A virus (HAV) is unaffordable to many developing countries. Substantial reductions in cost occur when vaccines are administered intradermally at low doses. Aluminum-free HAV vaccines are considered more suitable for intradermal use than traditional vaccines which can cause long-lasting local reactions. Thus, we compared the immunogenicity and safety of an aluminum-free virosomal HAV vaccine (Epaxal) administered by different routes: intradermal (i.d.), subcutaneous (s.c.), and intramuscular (i.m.). Two open pilot studies were conducted as sub-studies of a large lot consistency trial. Healthy subjects aged 18 to 45 were enrolled. Study 1 compared two i.d. regimens of a lower dose of Epaxal [0.1 mL (4.8 IU), one or two injection sites] with i.m. administration of the standard dose [0.5 mL (24 IU)]. Study 2 compared the s.c. with the i.m. administration of the standard dose. At month 12, subjects in study 1 received a booster dose of 0.1 mL i.d. or 0.5 mL i.m.; subjects in study 2 received 0.5 mL via the respective route (s.c. or i.m.). Serum was tested for antibodies at baseline, 2 weeks (study 1), and 1 and 6 months after the primary vaccination as well as prior and 1 month after the booster dose. Incidences of solicited and unsolicited adverse events were recorded. Seroprotection rates (anti-HAV geometric mean concentration of > or =20 mIU/mL) after 1 month ranged from 93.2% to 100% in all groups and remained high until month 12 (range 85.2&-90.2%). Complete (100%) seroprotection was achieved by all subjects in all groups after booster vaccination. All routes of administration were well tolerated. Local reactions were more common in subjects vaccinated i.d. and s.c. than i.m. The aluminum-free virosomal HAV vaccine Epaxal is highly immunogenic and well tolerated when administered either via i.d., s.c., or i.m. Vaccination via the i.d. route may confer significant cost savings over the conventional i.m. route.

  10. Safety and immunogenicity of chromatographically purified Vero cell rabies vaccine for intradermal pre- and post-exposure rabies prophylaxis.

    Science.gov (United States)

    Tantawichien, Terapong; Sibunruang, Suda; Tantawichien, Thanphet; Angsanakul, Jaruboot; Benjavongkulchai, Maneerat; Limsuwan, Kornvika; Udomchaisakul, Piyada; Khomvilai, Sumana; Sitprija, Visith

    2014-12-01

    Improved rabies pre- and post-exposure prophylaxis (PrEP and PEP) in developing countries uses an economic multi-site intradermal vaccination. To evaluate immunogenicity of chromatographically purified Vero cell vaccine (CPRV) for intradermal PrEP and PEP. The subjects received conventional PrEP with CPRV or PVRV in PrEP study or received intradermal PEP with CPRV or PVRV and rabies immunoglobulin in PEP study. All subjects who received PrEP with CPRV had protective neutralizing antibody (Nab) titers (≥0.5 IU/ml) 14 days after completing vaccination. In PEP study, Nab titers in the CPRV groups reached ≥ 0.5 IU/ml in all subjects by day 14 through day 90 after vaccination. The geometric mean titers of Nab in the CPRV groups had significantly higher titers than the PVRV group on day 14 through day 365 (p < 0.05). No serious adverse reactions were observed. CPRV is safe and immunogenic when given for intradermal PrEP and PEP.

  11. A combination trial of intradermal radiofrequency and hyaluronic acid filler for the treatment of nasolabial fold wrinkles: a pilot study.

    Science.gov (United States)

    Choi, Sun Young; Lee, Yong Hee; Kim, Hyuk; Koh, Hyun-Ju; Park, Sun-Young; Park, Won-Seok; Bae, Il-Hong; Park, Kui Young; Kim, Beom Joon

    2014-01-01

    Within the last few years, hyaluronic acid (HA) fillers and radiofrequency (RF) devices have shown significant promise for skin rejuvenation. But the effects of HA only lasted for a relatively short duration. Therefore, we tried a new combination therapy of intradermal RF and HA filler. To evaluate the clinical efficacy of combination therapy of intradermal RF and HA filler for nasolabial fold (NLF) wrinkle reduction. Ten Korean female volunteers with mild to severe NLFs were enrolled. In the control group, five subjects were treated with HA filler alone. In the experimental group, the other five subjects were treated with intradermal RF prior to HA filler. Efficacy was evaluated based on the change on the Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS) from baseline. At 12 and 24 weeks after treatment, the experimental group showed significantly greater improvement in mean WSRS score compared to the control group. And two (40%) of the five patients in the experimental group achieved 'very much improved' and two (40%) showed 'much improved' at 12 weeks after treatment. Intradermal RF treatment prior to HA filler injection may provide synergistic and long-lasting effects for the reduction of NLF wrinkles.

  12. Skin reactions to human papillomavirus (HPV) 16 specific antigens intradermally injected in healthy subjects and patients with cervical neoplasia

    NARCIS (Netherlands)

    van den Hende, Muriel; van Poelgeest, Mariëtte I. E.; van der Hulst, Jeanette M.; de Jong, Joan; Drijfhout, Jan W.; Fleuren, Gert Jan; Valentijn, A. Rob P. M.; Wafelman, Amon R.; Slappendel, Gijs M.; Melief, Cornelis J. M.; Offringa, Rienk; van der Burg, Sjoerd H.; Kenter, Gemma G.

    2008-01-01

    We have tested the safety and feasibility of a synthetic long peptide-based HPV16-specific skin test to detect cellular immune responses to HPV16 E2, E6 and E7 in vivo. Women with cervical neoplasia (n = 11) and healthy individuals (n = 19) were intradermally challenged with 8 different pools of

  13. Immunogenicity and safety of low dose virosomal adjuvanted influenza vaccine administered intradermally compared to intramuscular full dose administration

    NARCIS (Netherlands)

    Künzi, Valérie; Klap, Jaco M.; Seiberling, Michael K.; Herzog, Christian; Hartmann, Katharina; Kürsteiner, Oliver; Kompier, Ronald; Grimaldi, Roberto; Goudsmit, Jaap

    2009-01-01

    BACKGROUND: Despite the established benefit of intramuscular (i.m.) influenza vaccination, new adjuvants and delivery methods for comparable or improved immunogenicity are being explored. Intradermal (i.d.) antigen administration is hypothesized to initiate an efficient immune response at reduced

  14. Influenza vaccination in healthcare workers; comparison of side effects and preferred route of administration of intradermal versus intramuscular administration.

    Science.gov (United States)

    Meijer, W J; Wensing, A M J; Bos, A A; Kuiphuis, J C F; Hagelen, E M M; Wilschut, J C; de Vries, M J T; Riezebos-Brilman, A

    2017-03-13

    To explore the nature and severity of side effects and future preference of intradermal versus intramuscular influenza vaccination in healthcare workers. Prospective cohort study. Two University Medical Centers in The Netherlands. Healthcare workers receiving an influenza vaccination. Healthcare workers that were vaccinated during the influenza vaccination season of 2012-2013 were approached for participation in a questionnaire study. The questionnaire was divided into two parts. The first part had to be answered directly after vaccination and the second part two weeks after vaccination. The motivation for vaccine uptake, whether or not the HCWs had direct contact with patients and the prevalence and severity of local and systemic side effects of influenza vaccination were explored. In addition, it was assessed how participants experienced the vaccination and which type of administration they preferred for future vaccination. Side effects of vaccination were more prevalent in the intradermal group versus the intramuscular group (56% versus 26%, pvaccine. Directly after vaccination, healthcare workers preferred the intradermal vaccination. Two weeks after vaccination both types of vaccine were equally appreciated. This study shows that there are significant differences in the nature and severity of side effects upon intramuscular and intradermal influenza vaccination. This difference did not result in a preference among the vaccinated subjects for one type of vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. An experimental infection model for Tetrameres americana (Cram 1927).

    Science.gov (United States)

    Fink, M; Permin, A; Jensen, K-M V; Bresciani, J; Magwisha, H B

    2005-02-01

    An experimental infection model for the heteroecious spiruid nematode Tetrameres americana (Cram 1927) was developed. The cockroach Blattella germanica (L.) and the locust Locusta migratoria (L.) were found to serve as intermediate hosts for the parasite. T. americana larvae developed to full maturity in these intermediate hosts and were infective to young Lohman Brown chickens after 32 days in the cockroach and 28 days in the locust. The maximum length of the larvae was reached in the insects at 28-30 degrees C after 10-15 days, at which time the larvae measured up to 2.2 mm. The parasite did not develop in the cockroach Periplaneta americana (L.), the woodlouse Oniscus asellus (L.), or the pupal stage of the giant mealworm Zophobas morio (Fabricius). Trials in which chickens were infected directly without an intermediate host failed. Infection of 24 chickens with a dosage of 100 larvae was followed by weekly post-mortems until day 48 post-infection (p.i.) and used to describe the development of T. americana. The average establishment rate (%) and the average worm burden varied from 16.5 to 30.8. The total numbers of parasites recovered ranged from 9 to 40. During mating, in the first 2 weeks p.i. females and males were equally abundant, whereas from day 20 p.i. twice as many females were recovered. From day 13 p.i. the females average length fluctuated between 2.6 and 3.7 mm, whereas they reached their maximum width of 2.4 mm on day 48 p.i. Males reached their full length after 27 days p.i. and measured up to 6.7 mm.

  16. Animal models of enterovirus 71 infection: applications and limitations

    Science.gov (United States)

    2014-01-01

    Human enterovirus 71 (EV71) has emerged as a neuroinvasive virus that is responsible for several outbreaks in the Asia-Pacific region over the past 15 years. Appropriate animal models are needed to understand EV71 neuropathogenesis better and to facilitate the development of effective vaccines and drugs. Non-human primate models have been used to characterize and evaluate the neurovirulence of EV71 after the early outbreaks in late 1990s. However, these models were not suitable for assessing the neurovirulence level of the virus and were associated with ethical and economic difficulties in terms of broad application. Several strategies have been applied to develop mouse models of EV71 infection, including strategies that employ virus adaption and immunodeficient hosts. Although these mouse models do not closely mimic human disease, they have been applied to determine the pathogenesis of and treatment and prevention of the disease. EV71 receptor-transgenic mouse models have recently been developed and have significantly advanced our understanding of the biological features of the virus and the host-parasite interactions. Overall, each of these models has advantages and disadvantages, and these models are differentially suited for studies of EV71 pathogenesis and/or the pre-clinical testing of antiviral drugs and vaccines. In this paper, we review the characteristics, applications and limitation of these EV71 animal models, including non-human primate and mouse models. PMID:24742252

  17. Semi-Analytic Solution of HIV and TB Co-Infection Model BOLARIN ...

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT In this work we developed and analyzed a mathematical model of HIV and TB co- infection. ... Jyota (2013) have developed mathematical models of ...... Infection Disease, 2(1):1-7. Silver, J C; Delfim, F M (2015). A mathematical modeling of TB-HIV/AIDS co infection and optimal control. Discrete and Continuous.

  18. A gastrointestinal rotavirus infection mouse model for immune modulation studies

    Directory of Open Access Journals (Sweden)

    van Amerongen Geert

    2011-03-01

    Full Text Available Abstract Background Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The current study was conducted to assess whether colostrum containing rotavirus-specific antibodies (Gastrogard-R® could protect against rotavirus infection. In addition, this illness model was used to study modulatory effects of intervention on several immune parameters after re-infection. Methods BALB/c mice were treated by gavage once daily with Gastrogard-R® from the age of 4 to 10 days, and were inoculated with rhesus rotavirus (RRV at 7 days of age. A secondary inoculation with epizootic-diarrhea infant-mouse (EDIM virus was administered at 17 days of age. Disease symptoms were scored daily and viral shedding was measured in fecal samples during the post-inoculation periods. Rotavirus-specific IgM, IgG and IgG subclasses in serum, T cell proliferation and rotavirus-specific delayed-type hypersensitivity (DTH responses were also measured. Results Primary inoculation with RRV induced a mild but consistent level of diarrhea during 3-4 days post-inoculation. All mice receiving Gastrogard-R® were 100% protected against rotavirus-induced diarrhea. Mice receiving both RRV and EDIM inoculation had a lower faecal-viral load following EDIM inoculation then mice receiving EDIM alone or Gastrogard-R®. Mice receiving Gastrogard-R® however displayed an enhanced rotavirus-specific T-cell proliferation whereas rotavirus-specific antibody subtypes were not affected. Conclusions Preventing RRV-induced diarrhea by Gastrogard-R® early in life showed a diminished protection against EDIM re-infection, but a rotavirus-specific immune response was developed including both B cell and T cell responses. In general, this intervention model can be used for studying clinical symptoms as well as the immune responses required for protection against viral re-infection.

  19. Development of a Zika Virus Infection Model in Cynomolgus Macaques

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    Fusataka Koide

    2016-12-01

    Full Text Available Limited availability of Indian rhesus macaques (IRM is a bottleneck to study Zika virus (ZIKV pathogenesis and evaluation of appropriate control measures in non-human primates. To address these issues, we report here the Mauritian cynomolgus macaque (MCM model for ZIKV infection. In brief, six MCMs (seronegative for dengue and ZIKV were subdivided into 3 cohorts with a male and female each and challenged with different doses of Asian PRVABC59 (Puerto Rico or FSS13025 (Cambodia or African (IBH30656 lineage ZIKV isolates. Clinical signs were monitored; and biological fluids (serum, saliva and urine and tissues (testes and brain were assessed for viral load by quantitative RT-PCR and neutralizing antibodies (Nab by 50% Plaque Reduction Neutralization Test (PRNT50 at various times post infection (p.i. PRVABC59 induced viremia detectable up to day 10, with peak viral load at 2 to 3 days p.i. An intermittent viremia spike was observed on day 30 with titers reaching 2.5 ×103 genomes/mL. Moderate viral load was observed in testes, urine and saliva. In contrast, FSS13025 induced viremia lasting only up to 6 days and detectable viral loads in testes but not in urine and saliva. Recurrent viremia was detected but at lower titers compare to PRVABC59. Challenge with either PRVABC59 or FSS13025 resulted in 100% seroconversion; with mean PRNT50 titers ranging from 597 to 5179. IBH30656 failed to establish infection in MCM suggesting that MCM are susceptible to infection with ZIKV isolates of the Asian lineage but not from Africa. Due to the similarity of biphasic viremia and Nab responses between MCM and IRM models, MCM could be a suitable alternative for evaluation of ZIKV vaccine and therapeutic candidates.

  20. Animal models for Ebola and Marburg virus infections

    Science.gov (United States)

    Nakayama, Eri; Saijo, Masayuki

    2013-01-01

    Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765

  1. Animal models for Ebola and Marburg virus infections

    Directory of Open Access Journals (Sweden)

    Eri eNakayama

    2013-09-01

    Full Text Available Ebola and Marburg hemorrhagic fevers (EHF and MHF are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus, respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4 pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using nonhuman primates (NHPs and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics.

  2. An integrated stewardship model : Antimicrobial, infection prevention and diagnostic (AID)

    NARCIS (Netherlands)

    Dik, Jan-Willem H.; Poelman, Randy; Friedrich, Alexander W.; Panday, Prashant Nannan; Lo-Ten-Foe, Jerome R.; van Assen, Sander; van Gemert-Pijnen, Julia E. W. C.; Niesters, Hubert G. M.; Hendrix, Ron; Sinha, Bhanu

    2016-01-01

    Considering the threat of antimicrobial resistance and the difficulties it entails in treating infections, it is necessary to cross borders and approach infection management in an integrated, multidisciplinary manner. We propose the antimicrobial, infection prevention and diagnostic stewardship

  3. An integrated stewardship model: antimicrobial, infection prevention and diagnostic (AID)

    NARCIS (Netherlands)

    Dik, Jan-Willem H.; Poelman, Randy; Friedrich, Alexander W.; Panday, Prashant N.; Lo-Ten-Foe, Jerome R.; van Assen, Sander; van Gemert-Pijnen, Julia E.W.C.; Niesters, Hubert G.M.; Hendrix, Ron; Sinha, Bhanu

    2015-01-01

    Considering the threat of antimicrobial resistance and the difficulties it entails in treating infections, it is necessary to cross borders and approach infection management in an integrated, multidisciplinary manner. We propose the antimicrobial, infection prevention and diagnostic stewardship

  4. Infections

    Science.gov (United States)

    ... Type b) How to Take Your Child's Temperature Impetigo Infant Botulism Infections That Pets Carry Influenza (Flu) ... Herpes Hand, Foot, and Mouth Disease Hives (Urticaria) Impetigo Infections That Pets Carry Lyme Disease Measles Molluscum ...

  5. Dengue human infection models to advance dengue vaccine development.

    Science.gov (United States)

    Larsen, Christian P; Whitehead, Stephen S; Durbin, Anna P

    2015-12-10

    Dengue viruses (DENV) currently infect approximately 400 million people each year causing millions to seek care and overwhelming the health care infrastructure in endemic areas. Vaccines to prevent dengue and therapeutics to treat dengue are not currently available. The efficacy of the most advanced candidate vaccine against symptomatic dengue in general and DENV-2 in particular was much lower than expected, despite the ability of the vaccine to induce neutralizing antibody against all four DENV serotypes. Because seroconversion to the DENV serotypes following vaccination was thought to be indicative of induced protection, these results have made it more difficult to assess which candidate vaccines should or should not be evaluated in large studies in endemic areas. A dengue human infection model (DHIM) could be extremely valuable to down-select candidate vaccines or therapeutics prior to engaging in efficacy trials in endemic areas. Two DHIM have been developed to assess the efficacy of live attenuated tetravalent (LATV) dengue vaccines. The first model, developed by the Laboratory of Infectious Diseases at the U. S. National Institutes of Health, utilizes a modified DENV-2 strain DEN2Δ30. This virus was derived from the DENV-2 Tonga/74 that caused only very mild clinical infection during the outbreak from which it was recovered. DEN2Δ30 induced viremia in 100%, rash in 80%, and neutropenia in 27% of the 30 subjects to whom it was given. The Walter Reed Army Institute of Research (WRAIR) is developing a DHIM the goal of which is to identify DENV that cause symptomatic dengue fever. WRAIR has evaluated seven viruses and has identified two that meet dengue fever criteria. Both of these models may be very useful in the evaluation and down-selection of candidate dengue vaccines and therapeutics. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Host Nectin-1 Promotes Chlamydial Infection in the Female Mouse Genital Tract, but Is Not Required for Infection in a Novel Male Murine Rectal Infection Model.

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    Jessica A Slade

    Full Text Available Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen, but more than 70% of patients fail to seek treatment due to the asymptomatic nature of these infections. Women suffer from numerous complications from chronic chlamydial infections, which include pelvic inflammatory disease and infertility. We previously demonstrated in culture that host cell nectin-1 knockdown significantly reduced chlamydial titers and inclusion size. Here, we sought to determine whether nectin-1 was required for chlamydial development in vivo by intravaginally infecting nectin-1-/- mice with Chlamydia muridarum and monitoring chlamydial shedding by chlamydial titer assay. We observed a significant reduction in chlamydial shedding in female nectin-1-/- mice compared to nectin-1+/+ control mice, an observation that was confirmed by PCR. Immunohistochemical staining in mouse cervical tissue confirmed that there are fewer chlamydial inclusions in Chlamydia-infected nectin-1-/- mice. Notably, anorectal chlamydial infections are becoming a substantial health burden, though little is known regarding the pathogenesis of these infections. We therefore established a novel male murine model of rectal chlamydial infection, which we used to determine whether nectin-1 is required for anorectal chlamydial infection in male mice. In contrast to the data from vaginal infection, no difference in rectal chlamydial shedding was observed when male nectin-1+/+ and nectin-1-/- mice were compared. Through the use of these two models, we have demonstrated that nectin-1 promotes chlamydial infection in the female genital tract but does not appear to contribute to rectal infection in male mice. These models could be used to further characterize tissue and sex related differences in chlamydial infection.

  7. Pathogenesis of Candida albicans infections in the alternative chorio-allantoic membrane chicken embryo model resembles systemic murine infections.

    Directory of Open Access Journals (Sweden)

    Ilse D Jacobsen

    Full Text Available Alternative models of microbial infections are increasingly used to screen virulence determinants of pathogens. In this study, we investigated the pathogenesis of Candida albicans and C. glabrata infections in chicken embryos infected via the chorio-allantoic membrane (CAM and analyzed the virulence of deletion mutants. The developing immune system of the host significantly influenced susceptibility: With increasing age, embryos became more resistant and mounted a more balanced immune response, characterized by lower induction of proinflammatory cytokines and increased transcription of regulatory cytokines, suggesting that immunopathology contributes to pathogenesis. While many aspects of the chicken embryo response resembled murine infections, we also observed significant differences: In contrast to systemic infections in mice, IL-10 had a beneficial effect in chicken embryos. IL-22 and IL-17A were only upregulated after the peak mortality in the chicken embryo model occurred; thus, the role of the Th17 response in this model remains unclear. Abscess formation occurs frequently in murine models, whereas the avian response was dominated by granuloma formation. Pathogenicity of the majority of 15 tested C. albicans deletion strains was comparable to the virulence in mouse models and reduced virulence was associated with significantly lower transcription of proinflammatory cytokines. However, fungal burden did not correlate with virulence and for few mutants like bcr1Δ and tec1Δ different outcomes in survival compared to murine infections were observed. C. albicans strains locked in the yeast stage disseminated significantly more often from the CAM into the embryo, supporting the hypothesis that the yeast morphology is responsible for dissemination in systemic infections. These data suggest that the pathogenesis of C. albicans infections in the chicken embryo model resembles systemic murine infections but also differs in some aspects. Despite

  8. Infection dynamics on spatial small-world network models

    Science.gov (United States)

    Iotti, Bryan; Antonioni, Alberto; Bullock, Seth; Darabos, Christian; Tomassini, Marco; Giacobini, Mario

    2017-11-01

    The study of complex networks, and in particular of social networks, has mostly concentrated on relational networks, abstracting the distance between nodes. Spatial networks are, however, extremely relevant in our daily lives, and a large body of research exists to show that the distances between nodes greatly influence the cost and probability of establishing and maintaining a link. A random geometric graph (RGG) is the main type of synthetic network model used to mimic the statistical properties and behavior of many social networks. We propose a model, called REDS, that extends energy-constrained RGGs to account for the synergic effect of sharing the cost of a link with our neighbors, as is observed in real relational networks. We apply both the standard Watts-Strogatz rewiring procedure and another method that conserves the degree distribution of the network. The second technique was developed to eliminate unwanted forms of spatial correlation between the degree of nodes that are affected by rewiring, limiting the effect on other properties such as clustering and assortativity. We analyze both the statistical properties of these two network types and their epidemiological behavior when used as a substrate for a standard susceptible-infected-susceptible compartmental model. We consider and discuss the differences in properties and behavior between RGGs and REDS as rewiring increases and as infection parameters are changed. We report considerable differences both between the network types and, in the case of REDS, between the two rewiring schemes. We conclude that REDS represent, with the application of these rewiring mechanisms, extremely useful and interesting tools in the study of social and epidemiological phenomena in synthetic complex networks.

  9. Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling

    DEFF Research Database (Denmark)

    Bodenlenz, Manfred; Höfferer, Christian; Magnes, Christoph

    2012-01-01

    BACKGROUND: Methodologies for continuous sampling of lipophilic drugs and high-molecular solutes in the dermis are currently lacking. We investigated the feasibility of sampling a lipophilic topical drug and the locally released biomarker in the dermis of non-lesional and lesional skin of psoriatic......OFM sampling was performed for 25 h from each site on day 1 and day 8. Patients were mobile as dOFM probes were operated by a novel light-weight push-pull pump. Ultrasound was used to verify intradermal probe placement, cap-LC-MS/MS for BCT194 and ELISA for TNFα analysis. RESULTS: dOFM was well tolerated......-channel pumps allowed prolonged intradermal PK/PD profiling of a lipophilic topical drug in psoriatic patients. This initial study shows that dOFM overcomes limitations of microdialysis sampling methodology, and it demonstrates the potential for PK/PD studies of topical products and formulations in a clinical...

  10. Usefulness of confocal microscopy in distinguishing between basal cell carcinoma and intradermal melanocytic nevus on the face.

    Science.gov (United States)

    Gamo, R; Floristan, U; Pampín, A; Caro, D; Pinedo, F; López-Estebaranz, J L

    2015-10-01

    The clinical distinction between basal cell carcinoma (BCC) and intradermal melanocytic nevus lesions on the face can be difficult, particularly in young patients or patients with multiple nevi. Dermoscopy is a useful tool for analyzing characteristic dermoscopic features of BCC, such as cartwheel structures, maple leaf-like areas, blue-gray nests and dots, and ulceration. It also reveals arborizing telangiectatic vessels and prominent curved vessels, which are typical of BCC, and comma vessels, which are typical of intradermal melanocytic nevi. It is, however, not always easy to distinguish between these 2 conditions, even when dermoscopy is used. We describe 2 facial lesions that posed a clinical and dermoscopic challenge in two 38-year-old patients; confocal microscopy showed separation between tumor nests and stroma and polarized nuclei, which are confocal microscopy features of basal cell carcinoma. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.

  11. Modeling the dynamics of Plasmodium vivax infection and hypnozoite reactivation in vivo.

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    Adeshina I Adekunle

    2015-03-01

    Full Text Available The dynamics of Plasmodium vivax infection is characterized by reactivation of hypnozoites at varying time intervals. The relative contribution of new P. vivax infection and reactivation of dormant liver stage hypnozoites to initiation of blood stage infection is unclear. In this study, we investigate the contribution of new inoculations of P. vivax sporozoites to primary infection versus reactivation of hypnozoites by modeling the dynamics of P. vivax infection in Thailand in patients receiving treatment for either blood stage infection alone (chloroquine, or the blood and liver stages of infection (chloroquine + primaquine. In addition, we also analysed rates of infection in a study in Papua New Guinea (PNG where patients were treated with either artesunate, or artesunate + primaquine. Our results show that up to 96% of the P. vivax infection is due to hypnozoite reactivation in individuals living in endemic areas in Thailand. Similar analysis revealed the around 70% of infections in the PNG cohort were due to hypnozoite reactivation. We show how the age of the cohort, primaquine drug failure, and seasonality may affect estimates of the ratio of primary P. vivax infection to hypnozoite reactivation. Modeling of P. vivax primary infection and hypnozoite reactivation provides important insights into infection dynamics, and suggests that 90-96% of blood stage infections arise from hypnozoite reactivation. Major differences in infection kinetics between Thailand and PNG suggest the likelihood of drug failure in PNG.

  12. Randomized single-blind clinical trial of intradermal methylene blue on pain reduction after open diathermy haemorrhoidectomy.

    Science.gov (United States)

    Sim, H-L; Tan, K-Y

    2014-08-01

    Open haemorrhoidectomy has been associated with considerable postoperative pain and discomfort. Perianal intradermal injection of methylene blue has been shown to ablate perianal nerve endings and may bring about temporary pain relief after haemorrhoidectomy. We hypothesized that the administration of intradermal methylene blue would reduce postoperative pain during the initial period after surgery. A randomized, prospective, single-blind placebo-controlled trial was conducted. Patients were randomized to intradermal injection at haemorrhoidectomy of either 4 ml 1% methylene blue and 16 ml 0.5% marcaine or of 16 ml 0.5% marcaine and 4 ml saline prior to surgical dissection. Patients were asked to fill in a pain diary with a visual analogue scale. The primary outcome measure was pain score and analgesic use. Secondary outcomes were complications. There were 37 patients in the methylene blue arm and 30 patients in the placebo arm. There were no statistically significant differences in the sex, type of haemorrhoid, number of haemorrhoids excised, duration of surgery or hospital stay. The mean pain scores were significantly lower and the use of paracetamol was also significantly less in the methylene blue group during the first three postoperative days. The risk ratio of acute urinary retention occurring when methylene blue was not used was 2.320 (95% CI 1.754-3.067). Other complication rates were not significantly different. Perianal intradermal injection of methylene blue was useful in reducing the initial postoperative pain of open haemorrhoidectomy. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  13. Protein phosphatase 2A regulates central sensitization in the spinal cord of rats following intradermal injection of capsaicin

    Directory of Open Access Journals (Sweden)

    Fang Li

    2006-03-01

    Full Text Available Abstract Background Intradermal injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A on the central nociceptive amplification process, which is induced by intradermal injection of capsaicin in rats. Results In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following intradermal injection of capsaicin in rats. Capsaicin injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer. Conclusion These findings indicate that PP2A plays an important role in the cellular mechanisms of spinal cord central sensitization induced by intradermal injection of capsaicin in rats, which may have implications in

  14. Antihistamines do not inhibit the wheal induced by the intradermal injection of autologous serum in resistant chronic idiopathic urticaria.

    Science.gov (United States)

    Magen, Eli; Mishal, Joseph; Zeldin, Yuri; Schlesinger, Menachem

    2012-01-01

    Some patients with chronic idiopathic urticaria (CIU) are resistant to conventional doses of antihistamines (AHs). This study was designed to check whether the skin wheal and flare reaction produced by the intradermal injection of autologous serum (AS) and by histamine differs in AH-resistant and AH responder CIU patients. CIU patients with treatment failure under fexofenadine at 180 mg q.d. increased their daily dose of AH to 4 tablets daily. Those with significant improvement of urticaria activity score under fexofenadine at 180 mg were included in the CIU group. Subjects with treatment failure despite a full 8-week fourfold fexofenadine treatment were included in the resistant CIU (R-CIU group). The control group consisted of sex- and age-matched patents with allergic rhinitis. The AS skin test and intradermal histamine-induced wheal and flare reaction were performed at baseline (without AH), after 8 and 16 weeks (under AH treatment). Forty-six subjects were included in the CIU group, 21 were in the R-CIU group, and 44 were in the control group. Under AH therapy, the skin reaction to intradermal histamine injection was significantly diminished in all study groups. In the R-CIU group, fexofenadine at 180 mg did not suppress AS-induced wheal reaction (5.96 ± 2.25 mm; p = 0.85), and with a fourfold AH dose some reduction of AS-induced wheal (3.79 ± 1.74 mm; p = 0.008) was observed but remained larger than in the CIU (2.31 ± 1.12; p = 0.006) and control groups (2.52 ± 1.36; p = 0.037). AHs do not inhibit the wheal induced by the intradermal injection of AS in R-CIU.

  15. Safety and Immunogenicity of purified chick embryo cell rabies vaccine (VaxiRab N) administered intradermally as post exposure prophylaxis.

    Science.gov (United States)

    Ravish, Hardanahalli S; Vijayashankar, Veena; Madhusudana, Shampur N; Sudarshan, Mysore K; Narayana, Doddabele Ha; Andanaiah, Gangaboraiah; Ashwin, Belludi Y; Rachana, Annadani R; Shamanna, Manjula

    2014-01-01

    The affordability to rabies vaccine for intramuscular administration in post exposure prophylaxis is a major constraint. Therefore, in countries, where there are financial constraints, World Health Organization recommends intradermal rabies vaccination that reduces the quantity and cost of vaccination. This study was done to evaluate the safety and immunogenicity of indigenously developed rabies vaccine (VaxiRab N) in comparison to a WHO recommended rabies vaccine (Rabipur) with demonstrated efficacy when administered by intradermal route using updated Thai Red Cross regimen. Eighty-six dog bite cases were randomly given either VaxiRab N (n = 43) or Rabipur (n = 43) as post exposure prophylaxis. The rabies virus neutralizing antibody concentrations on days 14, 28, 90, and 180 were tested by modified rapid fluorescent focus inhibition test. The geometric mean RVNA concentration of both the groups were compared using t- test and was found that, P value > 0.05 on all days, thus showing no significant difference between the 2 groups. The adverse drug events were also compared using Z-test and was found to be not statistically significant (Z = 1.476, P = 0.139). In conclusion, VaxiRab N was found to be safe and effective in post exposure prophylaxis by intradermal route and was similar to the WHO recommended rabies vaccine (Rabipur) of demonstrated efficacy.

  16. Hollow agarose microneedle with silver coating for intradermal surface-enhanced Raman measurements: a skin-mimicking phantom study

    Science.gov (United States)

    Yuen, Clement; Liu, Quan

    2015-06-01

    Human intradermal components contain important clinical information beneficial to the field of immunology and disease diagnosis. Although microneedles have shown great potential to act as probes to break the human skin barrier for the minimally invasive measurement of intradermal components, metal microneedles that include stainless steel could cause the following problems: (1) sharp waste production, and (2) contamination due to reuse of microneedles especially in developing regions. In this study, we fabricate agarose microneedles coated with a layer of silver (Ag) and demonstrate their use as a probe for the realization of intradermal surface-enhanced Raman scattering measurements in a set of skin-mimicking phantoms. The Ag-coated agarose microneedle quantifies a range of glucose concentrations from 5 to 150 mM inside the skin phantoms with a root-mean-square error of 5.1 mM within 10 s. The needle is found enlarged by 53.9% after another 6 min inside the phantom. The shape-changing capability of this agarose microneedle ensures that the reuse of these microneedles is impossible, thus avoiding sharp waste production and preventing needle contamination, which shows the great potential for safe and effective needle-based measurements.

  17. Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model

    Science.gov (United States)

    Laurie, Karen L.; Guarnaccia, Teagan A.; Carolan, Louise A.; Yan, Ada W. C.; Aban, Malet; Petrie, Stephen; Cao, Pengxing; Heffernan, Jane M.; McVernon, Jodie; Mosse, Jennifer; Kelso, Anne; McCaw, James M.; Barr, Ian G.

    2015-01-01

    Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1–14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season. PMID:25943206

  18. Tissue expansion and fluid absorption by skin tissue following intradermal injections through hollow microneedles

    Science.gov (United States)

    Shrestha, Pranav; Stoeber, Boris

    2017-11-01

    Hollow microneedles provide a promising alternative to conventional drug delivery techniques due to improved patient compliance and the dose sparing effect. The dynamics of fluid injected through hollow microneedles into skin, which is a heterogeneous and deformable porous medium, have not been investigated extensively in the past. We have introduced the use of Optical Coherence Tomography (OCT) for real-time visualization of fluid injections into excised porcine tissue. The results from ex-vivo experiments, including cross-sectional tissue images from OCT and pressure/flow-rate measurements, show a transient mode of high flow-rate into the tissue followed by a lower steady-state infusion rate. The injected fluid expands the underlying tissue and causes the external free surface of the skin to rise, forming a characteristic intradermal wheal. We have used OCT to visualize the evolution of tissue and free surface deformation, and advancement of the boundary between regions of expanding and stationary tissue. We will show the effect of different injection parameters such as fluid pressure, viscosity and microneedle retraction on the injected volume. This work has been supported through funding from the Collaborative Health Research Program by the Natural Science and Engineering Research Council of Canada and the Canadian Health Research Institute, and through the Canada Research Chairs program.

  19. Intradermal immunization with combined baculovirus and tumor cell lysate induces effective antitumor immunity in mice.

    Science.gov (United States)

    Kawahara, Mamoru; Takaku, Hiroshi

    2013-12-01

    Although tumor lysate contains all the potential helper and killer epitopes capable of stimulating T cells, it is difficult to use as a cancer vaccine because it suppresses dendritic cell (DC) function. We report that wild-type baculovirus possesses an adjuvant effect to improve the immunogenicity of tumor lysate. When mice were administered CT26 tumor cell lysate combined with baculovirus intradermally, antitumor immunity was induced and rejection of CT26 tumor growth was observed in 40% of the immunized mice. In contrast, such antitumor immunity was not elicited in mice inoculated with tumor cell lysate or baculovirus alone. In tumor-bearing mice, which had previously received the combined baculovirus and tumor lysate vaccine, the established tumors were completely eradicated by administering a booster dose of the combined vaccine. This antitumor effect was attributed to tumor-specific T cell immunity mediated primarily by CD8⁺ T cells. Baculovirus also strongly activated DCs loaded with tumor lysate. Increased interleukin (IL)-6 and IL-12p70 production were also observed in DCs co-cultured with tumor cell lysate and baculovirus. Our study demonstrates that combined baculovirus and tumor lysate vaccine can effectively stimulate DCs to induce acquired antitumor immunity.

  20. A blanching technique for intradermal injection of the hyaluronic acid Belotero.

    Science.gov (United States)

    Micheels, Patrick; Sarazin, Didier; Besse, Stéphanie; Sundaram, Hema; Flynn, Timothy C

    2013-10-01

    With the proliferation of dermal fillers in the aesthetic workplace have come instructions from various manufacturers regarding dermal placement. Determination of injection needle location in the dermis has in large part been based on physician expertise, product and needle familiarity, and patient-specific skin characteristics. An understanding of the precise depth of dermal structures may help practitioners improve injection specificity. Unlike other dermal fillers that suggest intradermal and deep dermal injection planes, a new hyaluronic acid with a cohesive polydensified matrix may be more appropriate for the superficial dermis because of its structure and its high degree of integration into the dermis. To that end, the authors designed a small study to quantify the depth of the superficial dermis by means of ultrasound and histology. Using ultrasound resources, the authors determined the depths of the epidermis, the dermis, and the reticular dermis in the buttocks of six patients; the authors then extrapolated the depth of the superficial reticular dermis. Histologic studies of two of the patients showed full integration of the product in the reticular dermis. Following determination of injection depths and filler integration, the authors describe a technique ("blanching") for injection of the cohesive polydensified matrix hyaluronic acid into the superficial dermis. At this time, blanching is appropriate only for injection of the cohesive polydensified matrix hyaluronic acid known as Belotero Balance in the United States, although it may have applications for other hyaluronic acid products outside of the United States.

  1. Efficacy and safety of a new intradermal PCV2 vaccine in pigs

    Directory of Open Access Journals (Sweden)

    M. Sno

    2016-01-01

    Vaccination with Porcilis® PCV ID resulted in small transient local reactions in a high percentage of the vaccinated animals with no temperature increase. In both the onset of immunity and duration of immunity challenge studies with PCV2 or M. hyopneumoniae, significant reduction of the PCV2 load in lymphoid tissue, lungs, serum and fecal swabs and M. hyopneumoniae-induced lung lesions were observed. In two field trials on two different farms where both PCV2 and M. hyopneumoniae were present, vaccination with Porcilis® PCV ID and/or Porcilis® M Hyo ID ONCE of 3 week old piglets resulted in a significant reduction of PCV2 viraemia, mortality and lung lesion scores at slaughter. In addition, a significant positive effect on average daily weight gain (between 44 and 59 g/day in the finishing phase was observed. The results support that this new intradermal vaccine is safe and efficacious against PCV2 and may be used concurrently with Porcilis® M Hyo ID ONCE.

  2. Rabies intradermal post-exposure vaccination of humans using reconstituted and stored vaccine.

    Science.gov (United States)

    Kamoltham, Thavachai; Khawplod, Pakamatz; Wilde, Henry

    2002-09-10

    Thailand's northern Petchabun province is endemic for canine rabies. There were 27 reported human rabies deaths between 1989 and 1998. A rabies control plan was formulated in 1997 between medical and veterinary public health officials. It started an intense education program and an ongoing dog vaccination campaign. Economic constraints and the high cost of biological were the main reasons for inadequate human post-exposure management (PET). It was therefore decided to use the economical Thai Red Cross Intradermal Vaccine Regimen (TRC-ID) throughout the province. The original TRC-ID method is only suitable for clinics that see more than one PET patient daily. TRC-ID was therefore modified by storing the reconstituted vaccine in a refrigerator for the same patient's next two visits. Data on a total of 8157 PET patients were collected. An additional modification of TRC-ID also eliminated the 90 day booster. There were no treatment failures and no human rabies deaths in 1999, 2000 and 2001. The modified TRC-ID method induces adequate levels of neutralizing antibodies, protects humans bitten by rabid dogs and results in significant savings in vaccine and travel costs.

  3. The Effects of Pregabalin and the Glial Attenuator Minocycline on the Response to Intradermal Capsaicin in Patients with Unilateral Sciatica

    Science.gov (United States)

    Sumracki, Nicole M.; Hutchinson, Mark R.; Gentgall, Melanie; Briggs, Nancy; Williams, Desmond B.; Rolan, Paul

    2012-01-01

    Background Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes. Aim This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg. Methods/Results Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 µg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce pre-capsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (−38% in affected leg, 95% CI for difference −19% to −52%). Both hand dominance and sex were significant covariates of response to capsaicin. Conclusions It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glial-mediated treatments for neuropathic pain. The differences in flare response between limbs may

  4. Agent-Based Modelling applied to 5D model of the HIV infection

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    Toufik Laroum

    2016-12-01

    The simplest model was the 3D mathematical model. But the complexity of this phenomenon and the diversity of cells and actors which affect its evolution requires the use of new approaches such as multi-agents approach that we have applied in this paper. The results of our simulator on the 5D model are promising because they are consistent with biological knowledge’s. Therefore, the proposed approach is well appropriate to the study of population dynamics in general and could help to understand and predict the dynamics of HIV infection.

  5. Intradermal drug delivery by low-frequency sonophoresis (25 kHz).

    Science.gov (United States)

    Santoianni, Pietro; Nino, Massimiliano; Calabro, Gabriella

    2004-10-15

    Ultrasound waves (US) have been proposed to facilitate the absorption of active compounds (transdermal delivery) stimulating some disaggregation of the horny layer and promoting convective movements within the epidermis. Drugs used for alopecia areata, melasma, and lentigo, although proved effective, have limited effects resulting from only partial penetration into the skin. This study has evaluated the efficacy of low-frequency sonophoresis (LFS) at 25 kHz produced by a sonicator apparatus for treatment of alopecia areata, melasma, and solar lentigo. Thirty patients affected by alopecia areata were treated by application of methylprednisolone or cyclosporine solution followed by LFS. In a case-control study 48 women with melasma and 48 with solar lentigo were also treated by depigmenting emulsion and LFS application. For alopecia areata after 36 applications with LFS and 3-month treatment, the results were 57 percent partial regrowth and 29 percent total with methylprednisolone, and 33 percent partial regrowth and 34 percent total when cyclosporine was used. For melasma and solar lentigines the results when the drug application was followed by LFS, were (after twice-a-week application for 3 months) 75 percent complete depigmentation and 25 percent partial for melasma, 43 percent total regression and 57 percent partial for solar lentigo. This is the first report of sonophoresis at a frequency of 25 kHz in dermatocosmetology. The study shows that LFS, a not aggressive technique, enhance penetration of topic agents obtaining effects at the level of the epidermis, dermis and appendages (intradermal delivery), giving better results in the treatment of some cosmetic skin disorders.

  6. Current Animal Models of Postoperative Spine Infection and Potential Future Advances

    Directory of Open Access Journals (Sweden)

    Alexandra eStavrakis

    2015-05-01

    Full Text Available Implant related infection following spine surgery is a devastating complication for patients and can potentially lead to significant neurological compromise, disability, morbidity, and even mortality. This paper provides an overview of the existing animal models of postoperative spine infection and highlights the strengths and weaknesses of each model. In addition there is discussion regarding potential modifications to these animal models to better evaluate preventative and treatment strategies for this challenging complication. Current models are effective in simulating surgical procedures but fail to evaluate infection longitudinally using multiple techniques. Potential future modifications to these models include using advanced imaging technologies to evaluate infection, use of bioluminescent bacterial species, and testing of novel treatment strategies against multiple bacterial strains. There is potential to establish a postoperative spine infection model using smaller animals, such as mice, as these would be a more cost-effective screening tool for potential therapeutic interventions.

  7. Murine model of BCG lung infection: Dynamics of lymphocyte ...

    Indian Academy of Sciences (India)

    Unknown

    pulmonary BCG infection. Few T cells in tracheal LN of BCG infected mice produce IFNγ, suggesting that maturational changes associated with migration to the lungs or residence in the lungs enhance the capability of some T cells to produce this cytokine. [Saxena R K, Weissman D, Simpson J and Lewis D M 2002 Murine ...

  8. Infection

    Science.gov (United States)

    2010-09-01

    Klebsiella pneumoniae ). Staphylococcus species is by far the most studied pathogen in musculoskeletal infections and can produce a multilayered biofilm...the immune system and may be involved in both the response to sepsis and malignancy. For example, in neonatal mice, BMP signaling is a normal part of

  9. Trickle or clumped infection process? A stochastic model for the infection process of the parasitic roundworm of humans, Ascaris lumbricoides.

    Science.gov (United States)

    Walker, Martin; Hall, Andrew; Basáñez, María-Gloria

    2010-10-01

    The importance of the mode of acquisition of infectious stages of directly-transmitted parasitic helminths has been acknowledged in population dynamics models; hosts may acquire eggs/larvae singly in a "trickle" type manner or in "clumps". Such models have shown that the mode of acquisition influences the distribution and dynamics of parasite loads, the stability of host-parasite systems and the rate of emergence of anthelmintic resistance, yet very few field studies have allowed these questions to be explored with empirical data. We have analysed individual worm weight data for the parasitic roundworm of humans, Ascaris lumbricoides, collected from a three-round chemo-expulsion study in Dhaka, Bangladesh, with the aim of discerning whether a trickle or a clumped infection process predominates. We found that hosts tend to harbour female worms of a similar weight, indicative of a clumped infection process, but acknowledged that unmeasured host heterogeneities (random effects) could not be completely excluded as a cause. Here, we complement our previous statistical analyses using a stochastic infection model to simulate sizes of individual A. lumbricoides infecting a population of humans. We use the intraclass correlation coefficient (ICC) as a quantitative measure of similarity among simulated worm sizes and explore the behaviour of this statistic under assumptions corresponding to trickle or clumped infections and unmeasured host heterogeneities. We confirm that both mechanisms are capable of generating aggregates of similar-sized worms, but that the particular pattern of ICCs described pre- and post-anthelmintic treatment in the data is more consistent with aggregation generated by clumped infections than by host heterogeneities alone. This provides support to the notion that worms may be acquired in clumps. We discuss our results in terms of the population biology of A. lumbricoides and highlight the significance of our modelling approach for the study of the

  10. Nonhuman Primate Models of Chikungunya Virus Infection and Disease (CHIKV NHP Model

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    Rebecca Broeckel

    2015-09-01

    Full Text Available Chikungunya virus (CHIKV is a positive-sense RNA virus transmitted by Aedes mosquitoes. CHIKV is a reemerging Alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. Huge epidemics and the rapid spread of CHIKV seen in India and the Indian Ocean region established CHIKV as a global health concern. This concern was further solidified by the recent incursion of the virus into the Western hemisphere, a region without pre-existing immunity. Nonhuman primates (NHPs serve as excellent animal models for understanding CHIKV pathogenesis and pre-clinical assessment of vaccines and therapeutics. NHPs present advantages over rodent models because they are a natural amplification host for CHIKV and they share significant genetic and physiological homology with humans. CHIKV infection in NHPs results in acute fever, rash, viremia and production of type I interferon. NHPs develop CHIKV-specific B and T-cells, generating neutralizing antibodies and CHIKV-specific CD4+ and CD8+ T-cells. CHIKV establishes a persistent infection in NHPs, particularly in cynomolgus macaques, because infectious virus could be recovered from spleen, liver, and muscle as late as 44 days post infection. NHPs are valuable models that are useful in preclinical testing of vaccines and therapeutics and uncovering the details of CHIKV pathogenesis.

  11. A Trichophyton Rubrum Infection Model Based on the Reconstructed Human Epidermis - Episkin®.

    Science.gov (United States)

    Liang, Pan-Pan; Huang, Xin-Zhu; Yi, Jin-Ling; Chen, Zhi-Rui; Ma, Han; Ye, Cong-Xiu; Chen, Xian-Yan; Lai, Wei; Chen, Jian

    2016-01-05

    Trichophyton rubrum represents the most common infectious fungus responsible for dermatophytosis in human, but the mechanism involved is still not completely understood. An appropriate model constructed to simulate host infection is the prerequisite to study the pathogenesis of dermatophytosis caused by T. rubrum. In this study, we intended to develop a new T. rubrum infection model in vitro, using the three-dimensional reconstructed epidermis - EpiSkin ®, and to pave the way for further investigation of the mechanisms involved in T. rubrum infection. The reconstructed human epidermis (RHE) was infected by inoculating low-dose (400 conidia) and high-dose (4000 conidia) T. rubrum conidia to optimize the infection dose. During the various periods after infection, the samples were processed for pathological examination and scanning electron microscopy (SEM) observation. The histological analysis of RHE revealed a fully differentiated epidermis with a functional stratum corneum, which was analogous to the normal human epidermis. The results of hematoxylin and eosin staining and the periodic acid-Schiff staining showed that the infection dose of 400 conidia was in accord with the pathological characteristics of host dermatophytosis caused by T. rubrum. SEM observations further exhibited the process of T. rubrum infection in an intuitionistic way. We established the T. rubrum infection model on RHE in vitro successfully. It is a promising model for further investigation of the mechanisms involved in T. rubrum infection.

  12. Bioeconomic modeling of lactational antimicrobial treatment of new bovine subclinical intramammary infections caused by contagious pathogens

    NARCIS (Netherlands)

    Borne, van den B.H.P.; Halasa, T.; Schaik, van G.; Hogeveen, H.; Nielen, M.

    2010-01-01

    This study determined the direct and indirect epidemiologic and economic effects of lactational treatment of new bovine subclinical intramammary infections (IMI) caused by contagious pathogens using an existing bioeconomic model. The dynamic and stochastic model simulated the dynamics of

  13. An in vitro model for dengue virus infection that exhibits human monocyte infection, multiple cytokine production and dexamethasone immunomodulation

    Directory of Open Access Journals (Sweden)

    Sônia Regina Nogueira Ignácio Reis

    2007-12-01

    Full Text Available An important cytokine role in dengue fever pathogenesis has been described. These molecules can be associated with haemorrhagic manifestations, coagulation disorders, hypotension and shock, all symptoms implicated in vascular permeability and disease worsening conditions. Several immunological diseases have been treated by cytokine modulation and dexamethasone is utilized clinically to treat pathologies with inflammatory and autoimmune ethiologies. We established an in vitro model with human monocytes infected by dengue virus-2 for evaluating immunomodulatory and antiviral activities of potential pharmaceutical products. Flow cytometry analysis demonstrated significant dengue antigen detection in target cells two days after infection. TNF-alpha, IFN-alpha, IL-6 and IL-10 are produced by in vitro infected monocytes and are significantly detected in cell culture supernatants by multiplex microbead immunoassay. Dexamethasone action was tested for the first time for its modulation in dengue infection, presenting optimistic results in both decreasing cell infection rates and inhibiting TNF-alpha, IFN-alpha and IL-10 production. This model is proposed for novel drug trials yet to be applyed for dengue fever.

  14. Dynamics of a Fractional Order HIV Infection Model with Specific Functional Response and Cure Rate

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    Adnane Boukhouima

    2017-01-01

    Full Text Available We propose a fractional order model in this paper to describe the dynamics of human immunodeficiency virus (HIV infection. In the model, the infection transmission process is modeled by a specific functional response. First, we show that the model is mathematically and biologically well posed. Second, the local and global stabilities of the equilibria are investigated. Finally, some numerical simulations are presented in order to illustrate our theoretical results.

  15. The effects of intradermal botulinum toxin type a injections on pain symptoms of patients with diabetic neuropathy

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    Majid Ghasemi

    2014-01-01

    Full Text Available Background: Considering the dramatic increasing rate of diabetes and consequently its related complications, most importantly diabetic peripheral neuropathy (DPN, challenges regarding proper treatment of DPN and its effect on the quality-of-life and care of diabetic patients, the aim of this current study is to evaluate the effect of intradermal botulinum toxin type A (BTX-A injections on pain symptoms of patients with diabetic neuropathic pain. Materials and Methods: In this randomized double-blind placebo-controlled clinical trial study, diabetic patients aged <70 years with neuropathic pain in both feet were enrolled. Diabetic neuropathy (DN in selected patients was diagnosed using DN4 questionnaire and nerve conduction velocity examinations. They randomized in two intervention (BTX-A injection/100 unit, N = 20 and placebo groups (normal saline injection, N = 20. The outcome of injection on diabetic neuropathic pain was assessed using neuropathy pain scale (NPS and visual analog scale (VAS score and compared in two studied groups. Results: There was no significant difference in DN4, NPS and VAS scales of studied population after intervention in the placebo group. Intradermal injection of BTX-A reduced NPS scores for all items except cold sensation (P = 0.05. It reduced DN4 scores for electric shocks, burning, pins and needles and brushing (P < 0.05. According to VAS scale 30% and 0% of patients in intervention and placebo groups have no pain after intervention (P = 0.01. Conclusion: Intradermal injection of BTX-A is a well-tolerated agent that has a significant effect on DPN pain.

  16. Dynamics of an HBV/HCV infection model with intracellular delay and cell proliferation

    Science.gov (United States)

    Zhang, Fengqin; Li, Jianquan; Zheng, Chongwu; Wang, Lin

    2017-01-01

    A new mathematical model of hepatitis B/C virus (HBV/HCV) infection which incorporates the proliferation of healthy hepatocyte cells and the latent period of infected hepatocyte cells is proposed and studied. The dynamics is analyzed via Pontryagin's method and a newly proposed alternative geometric stability switch criterion. Sharp conditions ensuring stability of the infection persistent equilibrium are derived by applying Pontryagin's method. Using the intracellular delay as the bifurcation parameter and applying an alternative geometric stability switch criterion, we show that the HBV/HCV infection model undergoes stability switches. Furthermore, numerical simulations illustrate that the intracellular delay can induce complex dynamics such as persistence bubbles and chaos.

  17. Modeling the effects of prior infection on vaccine efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D.J.; Forrest, S.; Ackley, D.H. [Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Computer Science; Perelson, A.S. [Los Alamos National Lab., NM (United States)

    1997-11-01

    We performed computer simulations to study the effects of prior infection on vaccine efficacy. We injected three antigens sequentially. The first antigen, designated the prior, represented a prior infection or vaccination. The second antigen, the vaccine, represented a single component of the trivalent influenza vaccine. The third antigen, the epidemic, represented challenge by an epidemic strain. For a fixed vaccine to epidemic strain cross-reactivities to the vaccine and to the epidemic strains. We found that, for many cross-reactivities, vaccination, when it had been preceded by a prior infection, provided more protection than vaccination alone. However, at some cross-reactivities, the prior infection reduced protection by clearing the vaccine before it had the chance to produce protective memory. The cross-reactivities between the prior, vaccine and epidemic strains played a major role in determining vaccine efficacy. This work has applications to understanding vaccination against viruses such as influenza that are continually mutating.

  18. Modeling Powassan virus infection in Peromyscus leucopus, a natural host.

    Directory of Open Access Journals (Sweden)

    Luwanika Mlera

    2017-01-01

    Full Text Available The tick-borne flavivirus, Powassan virus (POWV causes life-threatening encephalitis in humans in North America and Europe. POWV is transmitted by ixodid tick vectors that feed on small to medium-sized mammals, such as Peromyscus leucopus mice, which may serve as either reservoir, bridge or amplification hosts. Intraperitoneal and intracranial inoculation of 4-week old Peromyscus leucopus mice with 103 PFU of POWV did not result in overt clinical signs of disease. However, following intracranial inoculation, infected mice seroconverted to POWV and histopathological examinations revealed that the mice uniformly developed mild lymphocytic perivascular cuffing and microgliosis in the brain and spinal cord from 5 to 15 days post infection (dpi, suggesting an early inflammatory response. In contrast, intracranial inoculation of 4-week old C57BL/6 and BALB/c mice was lethal by 5 dpi. Intraperitoneal inoculation was lethal in BALB/c mice, but 40% (2/5 of C57BL/6 mice survived. We concluded that Peromyscus leucopus mice infected i.c. with a lethal dose of POWV support a limited infection, restricted to the central nervous system and mount an antibody response to the virus. However, they fail to develop clinical signs of disease and are able to control the infection. These results suggest the involvement of restriction factors, and the mechanism by which Peromyscus leucopus mice restrict POWV infection remains under study.

  19. Intradermal injection of an anti-Langerin-HIVGag fusion vaccine targets epidermal Langerhans cells in nonhuman primates and can be tracked in vivo.

    Science.gov (United States)

    Salabert, Nina; Todorova, Biliana; Martinon, Frédéric; Boisgard, Raphaël; Zurawski, Gerard; Zurawski, Sandra; Dereuddre-Bosquet, Nathalie; Cosma, Antonio; Kortulewski, Thierry; Banchereau, Jacques; Levy, Yves; Le Grand, Roger; Chapon, Catherine

    2016-03-01

    The development of new immunization strategies requires a better understanding of early molecular and cellular events occurring at the site of injection. The skin is particularly rich in immune cells and represents an attractive site for vaccine administration. Here, we specifically targeted vaccine antigens to epidermal Langerhans cells (LCs) using a fusion protein composed of HIV antigens and a monoclonal antibody targeting Langerin. We developed a fluorescence imaging approach to visualize, in vivo, the vaccine-targeted cells. Studies were performed in nonhuman primates (NHPs) because of their relevance as a model to assess human vaccines. We directly demonstrated that in NHPs, intradermally injected anti-Langerin-HIVGag specifically targets epidermal LCs and induces rapid changes in the LC network, including LC activation and migration out of the epidermis. Vaccine targeting of LCs significantly improved anti-HIV immune response without requirement of an adjuvant. Although the co-injection of the TLR-7/8 synthetic ligand, R-848 (resiquimod), with the vaccine, did not enhance significantly the antibody response, it stimulated recruitment of HLA-DR+ inflammatory cells to the site of immunization. This study allowed us to characterize the dynamics of early local events following the injection of a vaccine-targeted epidermal LCs and R-848. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Attenuated cutaneous microvascular function in healthy young African Americans: Role of intradermal l-arginine supplementation.

    Science.gov (United States)

    Kim, Kiyoung; Hurr, Chansol; Patik, Jordan C; Matthew Brothers, R

    2018-02-03

    It has been established that endothelial function in conduit vessels is reduced in young African Americans (AA) relative to Caucasian Americans (CA). However, less is known regarding endothelial function in microvasculature of young AA. We hypothesized that microvascular function in response to local heating of skin is attenuated in young AA relative to age-matched CA due largely to the lack of NO bioavailability, which is in turn improved by intradermal l-arginine supplementation and/or inhibition of arginase. Nine AA and nine CA adults participated in this study. Participants were instrumented with four microdialysis membranes in the cutaneous vasculature of one forearm and were randomly assigned to receive 1) lactated Ringer's solution as a control site; 2) 20 mM NG-nitro-l-arginine (l-NAME) to inhibit NO synthase activity; 3) 10 mM l-arginine to local supplement l-arginine; or 4) a combination of 5.0 mM (S)-(2‑boronoethyl)-l-cysteine-HCL (BEC) and 5.0 mM Nω-hydroxy-nor-l-arginine (nor-NOHA) at a rate of 2.0 μl/min to locally inhibit arginase activity. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux divided by mean arterial pressure. All CVC data were presented as a percentage of maximal CVC (%CVCmax) that was determined by maximal cutaneous vasodilation induced by 44 °C heating plus sodium nitroprusside administration. The response during the 42 °C local heating plateau was blunted in the AA at the control site (CA: 84 ± 12 vs. AA: 62 ± 6 vs. %CVCmax; P l-arginine site (Control: 62 ± 6 vs. l-arginine: 70 ± 18%CVCmax; P l-arginine, but not arginase inhibition, improves cutaneous microvascular responses to local heating in young AA relative to CA. Copyright © 2018. Published by Elsevier Inc.

  1. Feline immunodeficiency virus (FIV) infection in the cat as a model for HIV infection in man: FIV induced impairment of immune function.

    NARCIS (Netherlands)

    C.H.J. Siebelink (Kees); I-H. Chu (I-Hai); G.F. Rimmelzwaan (Guus); K. Weijer (Kees); R. van Herwijnen (Rob); P. Knell (Peter); H.F. Egberink (Herman); M.L. Bosch (Marnix); A.D.M.E. Osterhaus (Albert)

    1990-01-01

    textabstractTo assess the value of feline immunodeficiency virus (FIV) infection as a model for human immunodeficiency virus (HIV) infection in man, we studied the impairment of certain immunological functions following natural or experimental FIV infection. Proliferative responses of peripheral

  2. The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections

    NARCIS (Netherlands)

    Tangden, T.; Martin, V.; Felton, T.W.; Nielsen, E.I.; Marchand, S.; Bruggemann, R.J.M.; Bulitta, J.B.; Bassetti, M.; Theuretzbacher, U.; Tsuji, B.T.; Wareham, D.W.; Friberg, L.E.; Waele, J.J. De; Tam, V.H.; Roberts, J.A.

    2017-01-01

    Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed.

  3. Clinical trial of the intradermal administration of hepatitis B vaccine produced at the Department of Medical Research, Myanmar.

    Science.gov (United States)

    Kyi, Khin Pyone; Oo, Khin May; Htun, Moh Moh; Tun, Win Maw; Aye, Khin Khin; Oo, San San; Lwin, Khin Ohmar; Nyunt, Sandar

    2002-02-22

    A total of 280 apparently healthy volunteers were screened for hepatitis B (HB) markers out of which 49 subjects (17.5%) were positive for HB surface antigen (HBsAg) and 82 (29.3%) were positive for antibody to HBsAg (anti-HBs). Three doses of DMR-HB vaccine, 0.15 ml per dose were administered to 95 subjects, who were serologically negative for both HB markers. The vaccination was given by the intradermal route on the flexor surface of the left forearm, at 1 month intervals according to the 0, 1 and 2 months schedule. The subjects were carefully monitored to record any adverse reaction of the vaccine. Blood specimen was collected from each subject, 1 month after the second and third vaccinations, to determine the anti-HBs antibody response to the vaccine. The study results showed that local pain was the only side effect noted and protective antibodies (anti-HBs) were detected in 69 (72.6%) of the vaccinees after the second dose of the vaccine and 89 (93.6%) after the third dose of the vaccine. Thus the intradermal route, which would require approximately one-seventh of the standard dose, would be suitable for use in certain groups such as high risk adults, when the cost of the vaccine is the inhibiting factor for routine or mass vaccination.

  4. Intradermal administration of magnesium sulphate and magnesium chloride produces hypesthesia to mechanical but hyperalgesia to heat stimuli in humans

    Directory of Open Access Journals (Sweden)

    Ikemoto Tatsunori

    2009-08-01

    Full Text Available Abstract Background Although magnesium ions (Mg2+ are known to display many similar features to other 2+ charged cations, they seem to have quite an important and unique role in biological settings, such as NMDA blocking effect. However, the role of Mg2+ in the neural transmission system has not been studied as sufficiently as calcium ions (Ca2+. To clarify the sensory effects of Mg2+ in peripheral nervous systems, sensory changes after intradermal injection of Mg2+ were studied in humans. Methods Magnesium sulphate, magnesium chloride and saline were injected into the skin of the anterior region of forearms in healthy volunteers and injection-induced irritating pain ("irritating pain", for short, tactile sensation, tactile pressure thresholds, pinch-pain changes and intolerable heat pain thresholds of the lesion were monitored. Results Flare formation was observed immediately after magnesium sulphate or magnesium chloride injection. We found that intradermal injections of magnesium sulphate and magnesium chloride transiently caused irritating pain, hypesthesia to noxious and innocuous mechanical stimulations, whereas secondary hyperalgesia due to mechanical stimuli was not observed. In contrast to mechanical stimuli, intolerable heat pain-evoking temperature was significantly decreased at the injection site. In addition to these results, spontaneous pain was immediately attenuated by local cooling. Conclusion Membrane-stabilizing effect and peripheral NMDA-blocking effect possibly produced magnesium-induced mechanical hypesthesia, and extracellular cation-induced sensitization of TRPV1 channels was thought to be the primary mechanism of magnesium-induced heat hyperalgesia.

  5. Use of nonhuman primate models to investigate mechanisms of infection-associated preterm birth

    Science.gov (United States)

    Adams Waldorf, Kristina M.; Rubens, Craig E.; Gravett, Michael G.

    2010-01-01

    Preterm birth is the most important direct cause of neonatal mortality and remains a major challenge for obstetrics and global health. Intrauterine infection causes approximately 50% of early preterm births. Animal models using pregnant mice, rabbits, or sheep, demonstrate the key link between infection and premature birth, but differ in mechanisms of parturition and placental structure from humans. The nonhuman primate (NHP) is a powerful model which emulates many features of human placentation and parturition. The contributions of the NHP model to preterm birth research are reviewed emphasizing the role of infections, and potential development of preventative and therapeutic strategies. PMID:21040390

  6. Animal models for the study of hepatitis C virus infection and related liver disease

    DEFF Research Database (Denmark)

    Bukh, Jens

    2012-01-01

    Hepatitis C virus (HCV) causes liver-related death in more than 300,000 people annually. Treatments for patients with chronic HCV are suboptimal, despite the introduction of directly acting antiviral agents. There is no vaccine that prevents HCV infection. Relevant animal models are important...... for HCV research and development of drugs and vaccines. Chimpanzees are the best model for studies of HCV infection and related innate and adaptive host immune responses. They can be used in immunogenicity and efficacy studies of HCV vaccines. The only small animal models of robust HCV infection are T...

  7. Foreign Body Infection Models to Study Host-Pathogen Response and Antimicrobial Tolerance of Bacterial Biofilm

    Directory of Open Access Journals (Sweden)

    Justyna Nowakowska

    2014-08-01

    Full Text Available The number of implanted medical devices is steadily increasing and has become an effective intervention improving life quality, but still carries the risk of infection. These infections are mainly caused by biofilm-forming staphylococci that are difficult to treat due to the decreased susceptibility to both antibiotics and host defense mechanisms. To understand the particular pathogenesis and treatment tolerance of implant-associated infection (IAI animal models that closely resemble human disease are needed. Applications of the tissue cage and catheter abscess foreign body infection models in the mouse will be discussed herein. Both models allow the investigation of biofilm and virulence of various bacterial species and a comprehensive insight into the host response at the same time. They have also been proven to serve as very suitable tools to study the anti-adhesive and anti-infective efficacy of different biomaterial coatings. The tissue cage model can additionally be used to determine pharmacokinetics, efficacy and cytotoxicity of antimicrobial compounds as the tissue cage fluid can be aspirated repeatedly without the need to sacrifice the animal. Moreover, with the advance in innovative imaging systems in rodents, these models may offer new diagnostic measures of infection. In summary, animal foreign body infection models are important tools in the development of new antimicrobials against IAI and can help to elucidate the complex interactions between bacteria, the host immune system, and prosthetic materials.

  8. Chronic hepatitis B infection and HBV DNA-containing capsids: Modeling and analysis

    Science.gov (United States)

    Manna, Kalyan; Chakrabarty, Siddhartha P.

    2015-05-01

    We analyze the dynamics of chronic HBV infection taking into account both uninfected and infected hepatocytes along with the intracellular HBV DNA-containing capsids and the virions. While previous HBV models have included either the uninfected hepatocytes or the intracellular HBV DNA-containing capsids, our model accounts for both these two populations. We prove the conditions for local and global stability of both the uninfected and infected steady states in terms of the basic reproduction number. Further, we incorporate a time lag in the model to encompass the intracellular delay in the production of the infected hepatocytes and find that this delay does not affect the overall dynamics of the system. The results for the model and the delay model are finally numerically illustrated.

  9. Brief report: biomarkers of aortic vascular prosthetic graft infection in a porcine model with Staphylococcus aureus

    DEFF Research Database (Denmark)

    Langerhuus, S. N.; Tønnesen, E. K.; Jensen, K. H.

    2010-01-01

    Aortic vascular prosthetic graft infection (AVPGI) with Staphylococcus aureus is a feared post-operative complication. This study was conducted to evaluate the clinical signs and potential biomarkers of infection in a porcine AVPGI model. The biomarkers evaluated were: C-reactive protein (CRP...

  10. Development of Chronic and Acute Golden Syrian Hamster Infection Models with Leptospira borgpetersenii serovar Hardjo

    Science.gov (United States)

    The golden Syrian hamster (Mesocricetus auratus) is frequently used as a model to study virulence for several species of Leptospira. Onset of an acute, lethal infection following infection with several pathogenic Leptospira species has been widely adopted for vaccine testing. An important exceptio...

  11. Management of childhood urinary tract infections: an economic modeling study.

    NARCIS (Netherlands)

    Harmsen, M.; Adang, E.M.M.; Wolters, R.J.; Wouden, J.C. van der; Grol, R.P.T.M.; Wensing, M.J.P.

    2009-01-01

    Childhood urinary tract infections (UTIs) can lead to renal scarring and ultimately to terminal renal failure, which has a high impact on quality of life, survival, and health-care costs. Variation in the treatment of UTIs between practices is high. OBJECTIVE: To assess the cost-effectiveness of a

  12. Development of a Mouse Model of Helicobacter pylori Infection that Mimics Human Disease

    Science.gov (United States)

    Marchetti, Marta; Arico, Beatrice; Burroni, Daniela; Figura, Natale; Rappuoli, Rino; Ghiara, Paolo

    1995-03-01

    The human pathogen Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. The pathogenesis of H. pylori infection in vivo was studied by adapting fresh clinical isolates of bacteria to colonize the stomachs of mice. A gastric pathology resembling human disease was observed in infections with cytotoxin-producing strains but not with noncytotoxic strains. Oral immunization with purified H. pylori antigens protected mice from bacterial infection. This mouse model will allow the development of therapeutic agents and vaccines against H. pylori infection in humans.

  13. Global analysis of viral infection in an archaeal model system

    Directory of Open Access Journals (Sweden)

    Walid S. Maaty

    2012-12-01

    Full Text Available The origin and evolutionary relationship of viruses is poorly understood. This makes archaeal virus-host of particular interest because the hosts generally root near the base of phylogenetic trees, while some of the viruses have clear structural similarities to those that infect prokaryotic and eukaryotic cells. Despite the advantageous position for use in evolutionary studies, little is known about archaeal viruses or how they interact with their hosts, compared to viruses of bacteria and eukaryotes. In addition, many archaeal viruses have been isolated from extreme environments and present a unique opportunity for elucidating factors that are important for existence at the extremes.. In this article we focus on virus-host interactions using a proteomics approach to study Sulfolobus Turreted Icosahedral Virus (STIV infection of Sulfolobus solfataricus P2. Using cultures grown from the ATCC cell stock, a single cycle of STIV infection was sampled 6 times over a 72 hr period. More than 700 proteins were identified throughout the course of the experiments. Seventy one host proteins were found to change by nearly two-fold (p<0.05 with 40 becoming more abundant and 31 less abundant. The modulated proteins represent 30 different cell pathways and 14 COG groups. 2D gel analysis showed that changes in post translational modifications were a common feature of the affected proteins. The results from these studies showed that the prokaryotic antiviral adaptive immune system CRISPR associated proteins (CAS proteins were regulated in response to the virus infection. It was found that regulated proteins come from mRNAs with a shorter than average half-life. In addition, activity-based protein profiling (ABPP profiling on 2D gels showed caspase, hydrolase and tyrosine phosphatase enzyme activity labeling at the protein isoform level. Together, this data provides a more detailed global view of archaeal cellular responses to viral infection, demonstrates the

  14. Mathematical modeling of transmission co-infection tuberculosis in HIV community

    Science.gov (United States)

    Lusiana, V.; Putra, P. S.; Nuraini, N.; Soewono, E.

    2017-03-01

    TB and HIV infection have the effect of deeply on assault the immune system, since they can afford to weaken host immune respone through a mechanism that has not been fully understood. HIV co-infection is the stongest risk factor for progression of M. tuberculosis to active TB disease in HIV individuals, as well as TB has been accelerated to progression HIV infection. In this paper we create a model of transmission co-infection TB in HIV community, dynamic system with ten compartments built in here. Dynamic analysis in this paper mentioned ranging from disease free equilibrium conditions, endemic equilibrium conditions, basic reproduction ratio, stability analysis and numerical simulation. Basic reproductive ratio were obtained from spectral radius the next generation matrix of the model. Numerical simulations are built to justify the results of the analysis and to see the changes in the dynamics of the population in each compartment. The sensitivity analysis indicates that the parameters affecting the population dynamics of TB in people with HIV infection is parameters rate of progression of individuals from the exposed TB class to the active TB, treatment rate of exposed TB individuals, treatment rate of infectious (active TB) individuals and probability of transmission of TB infection from an infective to a susceptible per contact per unit time. We can conclude that growing number of infections carried by infectious TB in people with HIV infection can lead to increased spread of disease or increase in endemic conditions.

  15. Immunobiology of congenital cytomegalovirus infection of the central nervous system—the murine cytomegalovirus model.

    Science.gov (United States)

    Slavuljica, Irena; Kveštak, Daria; Huszthy, Peter Csaba; Kosmac, Kate; Britt, William J; Jonjić, Stipan

    2015-03-01

    Congenital human cytomegalovirus infection is a leading infectious cause of long-term neurodevelopmental sequelae, including mental retardation and hearing defects. Strict species specificity of cytomegaloviruses has restricted the scope of studies of cytomegalovirus infection in animal models. To investigate the pathogenesis of congenital human cytomegalovirus infection, we developed a mouse cytomegalovirus model that recapitulates the major characteristics of central nervous system infection in human infants, including the route of neuroinvasion and neuropathological findings. Following intraperitoneal inoculation of newborn animals with mouse cytomegalovirus, the virus disseminates to the central nervous system during high-level viremia and replicates in the brain parenchyma, resulting in a focal but widespread, non-necrotizing encephalitis. Central nervous system infection is coupled with the recruitment of resident and peripheral immune cells as well as the expression of a large number of pro-inflammatory cytokines. Although infiltration of cellular constituents of the innate immune response characterizes the early immune response in the central nervous system, resolution of productive infection requires virus-specific CD8(+) T cells. Perinatal mouse cytomegalovirus infection results in profoundly altered postnatal development of the mouse central nervous system and long-term motor and sensory disabilities. Based on an enhanced understanding of the pathogenesis of this infection, prospects for novel intervention strategies aimed to improve the outcome of congenital human cytomegalovirus infection are proposed.

  16. Stability Analysis Susceptible, Exposed, Infected, Recovered (SEIR) Model for Spread Model for Spread of Dengue Fever in Medan

    Science.gov (United States)

    Side, Syafruddin; Molliq Rangkuti, Yulita; Gerhana Pane, Dian; Setia Sinaga, Marlina

    2018-01-01

    Dengue fever is endemic disease which spread through vector, Aedes Aegypty. This disease is found more than 100 countries, such as, United State, Africa as well Asia, especially in country that have tropic climate. Mathematical modeling in this paper, discusses the speed of the spread of dengue fever. The model adopting divided over four classes, such as Susceptible (S), Exposed (E), Infected (I) and Recovered (R). SEIR model further analyzed to detect the re-breeding value based on the number reported case by dengue in Medan city. Analysis of the stability of the system in this study is asymptotically stable indicating a case of endemic and unstable that show cases the endemic cases. Simulation on the mathematical model of SEIR showed that require a very long time to produce infected humans will be free of dengue virus infection. This happens because of dengue virus infection that occurs continuously between human and vector populations.

  17. Anti-infection activity of nanostructured titanium percutaneous implants with a postoperative infection model

    Science.gov (United States)

    Tan, Jing; Li, Yiting; Liu, Zhiyuan; Qu, Shuxin; Lu, Xiong; Wang, Jianxin; Duan, Ke; Weng, Jie; Feng, Bo

    2015-07-01

    The titanium percutaneous implants were widely used in clinic; however, they have an increased risk of infection since they breach the skin barrier. Lack of complete skin integration with the implants can cause infection and implant removal. In this work, three titania nanotubes (TNT) with different diameters, 50 nm (TNT-50), 100 nm (TNT-100) and 150 nm (TNT-150) arrays were prepared on titanium surfaces by anodization, pure titanium (pTi) was used as control. Samples were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and contact angle analysis. The antibacterial efficiency of TNT was evaluated in vitro against Staphylococcus aureus under the visible light. The results indicated that TNT-100 had the highest antibacterial efficiency under the visible light. Subsequently, TNT implants and pTi implants were placed subcutaneously to the dorsum of New Zealand White rabbits, 108 CFU S. aureus was inoculated into the implant sites 4 h after surgery. The TNF-alpha and IL-1alpha were determined using enzyme linked immunoassay (ELISA). TNT implants revealed less inflammatory factor release than pTi implants with or without injected S. aureus liquid. According to the histological results, the TNT implants displayed excellent tissue integration. Whereas, pTi implants were surrounded with fibrotic capsule, and the skin tissue was almost separated from the implant surface. Therefore, the TNT significantly inhibited the infection risk and enhanced tissue integration of the percutaneous implants compared to pTi. The immersion test in the culture medium suggested that one of causes be probably more proteins adsorbed on TNT than on pTi.

  18. Anti-infection activity of nanostructured titanium percutaneous implants with a postoperative infection model

    International Nuclear Information System (INIS)

    Tan, Jing; Li, Yiting; Liu, Zhiyuan; Qu, Shuxin; Lu, Xiong; Wang, Jianxin; Duan, Ke; Weng, Jie; Feng, Bo

    2015-01-01

    Highlights: • We prepared three titania nanotubes (TNT-50, TNT-100, TNT-150) on titanium surfaces by anodization. • TNT-100 had the highest antibacterial efficiency under the visible light. • The immersion test in the culture medium suggested that TNT can adsorb more proteins than pTi. • TNT implants inhibited the infection risk and enhanced tissue integration of the percutaneous implants compared to pTi. - Abstract: The titanium percutaneous implants were widely used in clinic; however, they have an increased risk of infection since they breach the skin barrier. Lack of complete skin integration with the implants can cause infection and implant removal. In this work, three titania nanotubes (TNT) with different diameters, 50 nm (TNT-50), 100 nm (TNT-100) and 150 nm (TNT-150) arrays were prepared on titanium surfaces by anodization, pure titanium (pTi) was used as control. Samples were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and contact angle analysis. The antibacterial efficiency of TNT was evaluated in vitro against Staphylococcus aureus under the visible light. The results indicated that TNT-100 had the highest antibacterial efficiency under the visible light. Subsequently, TNT implants and pTi implants were placed subcutaneously to the dorsum of New Zealand White rabbits, 10 8 CFU S. aureus was inoculated into the implant sites 4 h after surgery. The TNF-alpha and IL-1alpha were determined using enzyme linked immunoassay (ELISA). TNT implants revealed less inflammatory factor release than pTi implants with or without injected S. aureus liquid. According to the histological results, the TNT implants displayed excellent tissue integration. Whereas, pTi implants were surrounded with fibrotic capsule, and the skin tissue was almost separated from the implant surface. Therefore, the TNT significantly inhibited the infection risk and enhanced tissue integration of the percutaneous implants compared to pTi. The

  19. Anti-infection activity of nanostructured titanium percutaneous implants with a postoperative infection model

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Jing; Li, Yiting; Liu, Zhiyuan; Qu, Shuxin; Lu, Xiong; Wang, Jianxin; Duan, Ke; Weng, Jie; Feng, Bo, E-mail: fengbo@swjtu.edu.cn

    2015-07-30

    Highlights: • We prepared three titania nanotubes (TNT-50, TNT-100, TNT-150) on titanium surfaces by anodization. • TNT-100 had the highest antibacterial efficiency under the visible light. • The immersion test in the culture medium suggested that TNT can adsorb more proteins than pTi. • TNT implants inhibited the infection risk and enhanced tissue integration of the percutaneous implants compared to pTi. - Abstract: The titanium percutaneous implants were widely used in clinic; however, they have an increased risk of infection since they breach the skin barrier. Lack of complete skin integration with the implants can cause infection and implant removal. In this work, three titania nanotubes (TNT) with different diameters, 50 nm (TNT-50), 100 nm (TNT-100) and 150 nm (TNT-150) arrays were prepared on titanium surfaces by anodization, pure titanium (pTi) was used as control. Samples were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and contact angle analysis. The antibacterial efficiency of TNT was evaluated in vitro against Staphylococcus aureus under the visible light. The results indicated that TNT-100 had the highest antibacterial efficiency under the visible light. Subsequently, TNT implants and pTi implants were placed subcutaneously to the dorsum of New Zealand White rabbits, 10{sup 8} CFU S. aureus was inoculated into the implant sites 4 h after surgery. The TNF-alpha and IL-1alpha were determined using enzyme linked immunoassay (ELISA). TNT implants revealed less inflammatory factor release than pTi implants with or without injected S. aureus liquid. According to the histological results, the TNT implants displayed excellent tissue integration. Whereas, pTi implants were surrounded with fibrotic capsule, and the skin tissue was almost separated from the implant surface. Therefore, the TNT significantly inhibited the infection risk and enhanced tissue integration of the percutaneous implants compared to pTi. The

  20. Inhibition of Dermatophilus congolensis infection in a mouse model by antibiotic-producing staphylococci.

    OpenAIRE

    Noble, W. C.; Lloyd, D. H.; Appiah, S. N.

    1980-01-01

    In an acute model of skin infection with Dermatophilus congolensis in the mouse, lesions can be prevented by simultaneous application of staphylococci which produce antibiotics; non-producer staphylococci fail to inhibit lesion formation.

  1. Inhibition of Dermatophilus congolensis infection in a mouse model by antibiotic-producing staphylococci.

    Science.gov (United States)

    Noble, W C; Lloyd, D H; Appiah, S N

    1980-12-01

    In an acute model of skin infection with Dermatophilus congolensis in the mouse, lesions can be prevented by simultaneous application of staphylococci which produce antibiotics; non-producer staphylococci fail to inhibit lesion formation.

  2. Pharmacokinetics-Pharmacodynamics of Gatifloxacin in a Lethal Murine Bacillus Anthracis Inhalation Infection Model

    National Research Council Canada - National Science Library

    Ambrose, Paul G; Forrest, Alan; Craig, William A; Rubino, Christopher M; Bhavnani, Sujata M; Drusano, George L; Heine, Henery S

    2007-01-01

    We determined the pharmacokinetic-pharmacodynamic (PK-PD) measure most predictive of gatifloxacin efficacy and the magnitude of this measure necessary for survival in a murine Bacillus anthracis inhalation infection model...

  3. Putative biomarkers for evaluating antibiotic treatment: an experimental model of porcine Actinobacillus pleuropneumoniae infection

    DEFF Research Database (Denmark)

    Lauritzen, B.; Lykkesfeldt, J.; Skaanild, M.T.

    2003-01-01

    Biomarkers of infection were screened for their possible role as evaluators of antibiotic treatment in an aerosol infection model of porcine pneumonia caused by Actinobacillus pleuropneumoniae (Ap). Following infection of 12 pigs, clinical signs of pneumonia developed within 20 h, whereafter...... antibiotic treatment of acute Ap-infection ill pigs. The present model provides a valuable tool in the evaluation of antibiotic treatments, offering the advantage of clinical and pathological examinations combined with the use of biochemical infection markers....... the animals received a single dose of either danofloxacin (2.5 mg/kg) or tiamulin (10 mg/kg). To test the discriminative properties of the biomarkers, the dosage regimens were designed with an expected difference in therapeutic efficacy in favour of danofloxacin. Accordingly, the danofloxacin-treated pigs...

  4. Simulating transmission and control of Taenia solium infections using a reed-frost stochastic model

    DEFF Research Database (Denmark)

    Kyvsgaard, Niels Chr.; Johansen, Maria Vang; Carabin, Hélène

    2007-01-01

    The transmission dynamics of the human-pig zoonotic cestode Taenia solium are explored with both deterministic and stochastic versions of a modified Reed-Frost model. This model, originally developed for microparasitic infections (i.e. bacteria, viruses and protozoa), assumes that random contacts...... humans eating under-cooked pork meat harbouring T. solium metacestodes. Deterministic models of each scenario were first run, followed by stochastic versions of the models to assess the likelihood of infection elimination in the small population modelled. The effects of three groups of interventions were...

  5. A quantitative model for dermal infection and oedema in BALB/c mice pinna.

    Science.gov (United States)

    Marino-Marmolejo, Erika Nahomy; Flores-Hernández, Flor Yohana; Flores-Valdez, Mario Alberto; García-Morales, Luis Felipe; González-Villegas, Ana Cecilia; Bravo-Madrigal, Jorge

    2016-12-12

    Pharmaceutical industry demands innovation for developing new molecules to improve effectiveness and safety of therapeutic medicines. Preclinical assays are the first tests performed to evaluate new therapeutic molecules using animal models. Currently, there are several models for evaluation of treatments, for dermal oedema or infection. However, the most common or usual way is to induce the inflammation with chemical substances instead of infectious agents. On the other hand, this kind of models require the implementation of histological techniques and the interpretation of pathologies to verify the effectiveness of the therapy under assessment. This work was focused on developing a quantitative model of infection and oedema in mouse pinna. The infection was achieved with a strain of Streptococcus pyogenes that was inoculated in an injury induced at the auricle of BALB/c mice, the induced oedema was recorded by measuring the ear thickness with a digital micrometer and histopathological analysis was performed to verify the damage. The presence of S. pyogenes at the infection site was determined every day by culture. Our results showed that S. pyogenes can infect the mouse pinna and that it can be recovered at least for up to 4 days from the infected site; we also found that S. pyogenes can induce a bigger oedema than the PBS-treated control for at least 7 days; our results were validated with an antibacterial and anti-inflammatory formulation made with ciprofloxacin and hydrocortisone. The model we developed led us to emulate a dermal infection and allowed us to objectively evaluate the increase or decrease of the oedema by measuring the thickness of the ear pinna, and to determine the presence of the pathogen in the infection site. We consider that the model could be useful for assessment of new anti-inflammatory or antibacterial therapies for dermal infections.

  6. An agent-based model for Leishmania major infection

    Science.gov (United States)

    Dancik, Garrett M.; Jones, Douglas E.; Dorman, Karin S.

    Leishmania are protozoan parasites transmitted by bites of infected sandflies. Over 20 species of Leishmania, endemic in 88 countries, are capable of causing human disease. Disease is either cutaneous, where skin ulcers occur on exposed surfaces of the body, or visceral, with near certain mortality if untreated. C3HeB/FeJ mice are resistant to L. major, but develop chronic cutaneous lesions when infected with another species L. amazonensis. The well-characterized mechanism of resistance to L. major depends on a CD4+ Thl immune response, macrophage activation, and elimination of the parasite [Sacks 2002]. The factors that account for host susceptibility to L. Amazonensis, however, are not completely understood, despite being generally attributed to a weakened Th1 response [Vanloubbeck 2004].

  7. A periodic two-patch SIS model with time delay and transport-related infection.

    Science.gov (United States)

    Liu, Junli; Bai, Zhenguo; Zhang, Tailei

    2018-01-21

    In this paper, we propose a periodic SIS epidemic model with time delay and transport-related infection in a patchy environment. The basic reproduction number R 0 is derived which determines the global dynamics of the model system: if R 0   1. Numerical simulations are performed to confirm the analytical results and to explore the dependence of R 0 on the transport-related infection parameters and the amplitude of fluctuations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. The chicken as a natural model for extraintestinal infections caused by avian pathogenic Escherichia coli (APEC).

    Science.gov (United States)

    Antão, Esther-Maria; Glodde, Susanne; Li, Ganwu; Sharifi, Reza; Homeier, Timo; Laturnus, Claudia; Diehl, Ines; Bethe, Astrid; Philipp, Hans-C; Preisinger, Rudolf; Wieler, Lothar H; Ewers, Christa

    2008-01-01

    E. coli infections in avian species have become an economic threat to the poultry industry worldwide. Several factors have been associated with the virulence of E. coli in avian hosts, but no specific virulence gene has been identified as being entirely responsible for the pathogenicity of avian pathogenic E. coli (APEC). Needless to say, the chicken would serve as the best model organism for unravelling the pathogenic mechanisms of APEC, an extraintestinal pathogen. Five-week-old white leghorn SPF chickens were infected intra-tracheally with a well characterized APEC field strain IMT5155 (O2:K1:H5) using different doses corresponding to the respective models of infection established, that is, the lung colonization model allowing re-isolation of bacteria only from the lung but not from other internal organs, and the systemic infection model. These two models represent the crucial steps in the pathogenesis of APEC infections, including the colonization of the lung epithelium and the spread of bacteria throughout the bloodstream. The read-out system includes a clinical score, pathomorphological changes and bacterial load determination. The lung colonization model has been established and described for the first time in this study, in addition to a comprehensive account of a systemic infection model which enables the study of severe extraintestinal pathogenic E. coli (ExPEC) infections. These in vivo models enable the application of various molecular approaches to study host-pathogen interactions more closely. The most important application of such genetic manipulation techniques is the identification of genes required for extraintestinal virulence, as well as host genes involved in immunity in vivo. The knowledge obtained from these studies serves the dual purpose of shedding light on the nature of virulence itself, as well as providing a route for rational attenuation of the pathogen for vaccine construction, a measure by which extraintestinal infections, including

  9. Statistical inference and modelling for nosocomial infections and the incorporation of whole genome sequence data

    OpenAIRE

    Worby, Colin J.

    2013-01-01

    Healthcare-associated infections (HCAIs) remain a problem worldwide, and can cause severe illness and death. The increasing level of antibiotic resistance among bacteria that cause HCAIs limits infection treatment options, and is a major concern. Statistical modelling is a vital tool in developing an understanding of HCAI transmission dynamics. In this thesis, stochastic epidemic models are developed and used with the aim of investigating methicillin-resistant Staphylococcus aureus (MRSA) tra...

  10. Proteomic modeling for HIV-1 infected microglia-astrocyte crosstalk.

    Directory of Open Access Journals (Sweden)

    Tong Wang

    Full Text Available HIV-1-infected and immune competent brain mononuclear phagocytes (MP; macrophages and microglia secrete cellular and viral toxins that affect neuronal damage during advanced disease. In contrast, astrocytes can affect disease by modulating the nervous system's microenvironment. Interestingly, little is known how astrocytes communicate with MP to influence disease.MP-astrocyte crosstalk was investigated by a proteomic platform analysis using vesicular stomatitis virus pseudotyped HIV infected murine microglia. The microglial-astrocyte dialogue was significant and affected microglial cytoskeleton by modulation of cell death and migratory pathways. These were mediated, in part, through F-actin polymerization and filament formation. Astrocyte secretions attenuated HIV-1 infected microglia neurotoxicity and viral growth linked to the regulation of reactive oxygen species.These observations provide unique insights into glial crosstalk during disease by supporting astrocyte-mediated regulation of microglial function and its influence on the onset and progression of neuroAIDS. The results open new insights into previously undisclosed pathogenic mechanisms and open the potential for biomarker discovery and therapeutics that may influence the course of HIV-1-mediated neurodegeneration.

  11. Mathematical modeling applied to understand the host-pathogen interaction of HIV infection in Bangladesh

    Directory of Open Access Journals (Sweden)

    S. K. Sahani

    2017-10-01

    Full Text Available The most urgent public health problem today is to devise effective strategies to minimize the destruction caused by the AIDS epidemic. The understanding of HIV infection through mathematical modeling have made a significant contribution. The interaction of host to pathogen have been determined by fitting mathematical models to experimental data. In Bangladesh, the increasing rate of HIV infection comparing to the other countries of the world is not so high. Among the most at risk population of Bangladesh the HIV prevalent is still considered to be low with prevalence 1 then HIV infection persists.

  12. Multiplicity of Mathematical Modeling Strategies to Search for Molecular and Cellular Insights into Bacteria Lung Infection.

    Science.gov (United States)

    Cantone, Martina; Santos, Guido; Wentker, Pia; Lai, Xin; Vera, Julio

    2017-01-01

    Even today two bacterial lung infections, namely pneumonia and tuberculosis, are among the 10 most frequent causes of death worldwide. These infections still lack effective treatments in many developing countries and in immunocompromised populations like infants, elderly people and transplanted patients. The interaction between bacteria and the host is a complex system of interlinked intercellular and the intracellular processes, enriched in regulatory structures like positive and negative feedback loops. Severe pathological condition can emerge when the immune system of the host fails to neutralize the infection. This failure can result in systemic spreading of pathogens or overwhelming immune response followed by a systemic inflammatory response. Mathematical modeling is a promising tool to dissect the complexity underlying pathogenesis of bacterial lung infection at the molecular, cellular and tissue levels, and also at the interfaces among levels. In this article, we introduce mathematical and computational modeling frameworks that can be used for investigating molecular and cellular mechanisms underlying bacterial lung infection. Then, we compile and discuss published results on the modeling of regulatory pathways and cell populations relevant for lung infection and inflammation. Finally, we discuss how to make use of this multiplicity of modeling approaches to open new avenues in the search of the molecular and cellular mechanisms underlying bacterial infection in the lung.

  13. Intracellular hepatitis C modeling predicts infection dynamics and viral protein mechanisms.

    Science.gov (United States)

    Aunins, Thomas R; Marsh, Katherine A; Subramanya, Gitanjali; Uprichard, Susan L; Perelson, Alan S; Chatterjee, Anushree

    2018-03-21

    Hepatitis C virus infection is a global health problem, with nearly 2 million new infections occurring every year and up to 85% of these becoming chronic infections that pose serious long-term health risks. To effectively reduce the prevalence of HCV infection and associated diseases, it is important to understand the intracellular dynamics of the viral lifecycle. Here, we present a detailed mathematical model that represents the full hepatitis C lifecycle. It is the first full HCV model to be fit to acute intracellular infection data and the first to explore the functions of distinct viral proteins, probing multiple hypotheses of cis - and trans -acting mechanisms to provide insights for drug targeting. Model parameters were derived from the literature, experiments, and fitting to experimental intracellular viral RNA, extracellular viral titer, and HCV core and NS3 protein kinetic data from viral inoculation to steady-state. Our model predicts faster rates for protein translation and polyprotein cleavage than previous replicon models and demonstrates that the processes of translation and synthesis of viral RNA have the most influence on the levels of the species we tracked in experiments. Overall, our experimental data and the resulting mathematical infection model reveal information about the regulation of core protein during infection, produce specific insights into the roles of the viral core, NS5A, and NS5B proteins, and demonstrate the sensitivities of viral proteins and RNA to distinct reactions within the lifecycle. IMPORTANCE We have designed a model for the full lifecycle of hepatitis C virus. Past efforts have largely focused on modeling hepatitis C replicon systems, in which transfected subgenomic HCV RNA maintains autonomous replication in the absence of virion production or spread. We started with the general structure of these previous replicon models and expanded to create a model that incorporates the full virus lifecycle as well as additional

  14. A novel highly reproducible and lethal nonhuman primate model for orthopox virus infection.

    Directory of Open Access Journals (Sweden)

    Marit Kramski

    Full Text Available The intentional re-introduction of Variola virus (VARV, the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV and Monkeypox virus (MPXV cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus.A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1-3 days after onset of symptoms, even when very low infectious viral doses of 5x10(2 pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed.We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50 (minimal monkey infectious dose 50% of 8.3x10(2 pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis.

  15. Successful human infection with P. falciparum using three aseptic Anopheles stephensi mosquitoes: a new model for controlled human malaria infection.

    Directory of Open Access Journals (Sweden)

    Matthew B Laurens

    Full Text Available Controlled human malaria infection (CHMI is a powerful method for assessing the efficacy of anti-malaria vaccines and drugs targeting pre-erythrocytic and erythrocytic stages of the parasite. CHMI has heretofore required the bites of 5 Plasmodium falciparum (Pf sporozoite (SPZ-infected mosquitoes to reliably induce Pf malaria. We reported that CHMI using the bites of 3 PfSPZ-infected mosquitoes reared aseptically in compliance with current good manufacturing practices (cGMP was successful in 6 participants. Here, we report results from a subsequent CHMI study using 3 PfSPZ-infected mosquitoes reared aseptically to validate the initial clinical trial. We also compare results of safety, tolerability, and transmission dynamics in participants undergoing CHMI using 3 PfSPZ-infected mosquitoes reared aseptically to published studies of CHMI using 5 mosquitoes. Nineteen adults aged 18-40 years were bitten by 3 Anopheles stephensi mosquitoes infected with the chloroquine-sensitive NF54 strain of Pf. All 19 participants developed malaria (100%; 12 of 19 (63% on Day 11. The mean pre-patent period was 258.3 hours (range 210.5-333.8. The geometric mean parasitemia at first diagnosis by microscopy was 9.5 parasites/µL (range 2-44. Quantitative polymerase chain reaction (qPCR detected parasites an average of 79.8 hours (range 43.8-116.7 before microscopy. The mosquitoes had a geometric mean of 37,894 PfSPZ/mosquito (range 3,500-152,200. Exposure to the bites of 3 aseptically-raised, PfSPZ-infected mosquitoes is a safe, effective procedure for CHMI in malaria-naïve adults. The aseptic model should be considered as a new standard for CHMI trials in non-endemic areas. Microscopy is the gold standard used for the diagnosis of Pf malaria after CHMI, but qPCR identifies parasites earlier. If qPCR continues to be shown to be highly specific, and can be made to be practical, rapid, and standardized, it should be considered as an alternative for diagnosis

  16. Plasmid deficiency in urogenital isolates of Chlamydia trachomatis reduces infectivity and virulence in a mouse model.

    Science.gov (United States)

    Sigar, Ira M; Schripsema, Justin H; Wang, Yibing; Clarke, Ian N; Cutcliffe, Lesley T; Seth-Smith, Helena M B; Thomson, Nicholas R; Bjartling, Carina; Unemo, Magnus; Persson, Kenneth; Ramsey, Kyle H

    2014-02-01

    We hypothesized that the plasmid of urogenital isolates of Chlamydia trachomatis would modulate infectivity and virulence in a mouse model. To test this hypothesis, we infected female mice in the respiratory or urogenital tract with graded doses of a human urogenital isolate of C. trachomatis, serovar F, possessing the cognate plasmid. For comparison, we inoculated mice with a plasmid-free serovar F isolate. Following urogenital inoculation, the plasmid-free isolate displayed significantly reduced infectivity compared with the wild-type strain with the latter yielding a 17-fold lower infectious dose to yield 50% infection. When inoculated via the respiratory tract, the plasmid-free isolate exhibited reduced infectivity and virulence (as measured by weight change) when compared to the wild-type isolate. Further, differences in infectivity, but not in virulence were observed in a C. trachomatis, serovar E isolate with a deletion within the plasmid coding sequence 1 when compared to a serovar E isolate with no mutations in the plasmid. We conclude that plasmid loss reduces virulence and infectivity in this mouse model. These findings further support a role for the chlamydial plasmid in infectivity and virulence in vivo. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  17. Development of an in vivo model of Chlamydia abortus chronic infection in mice overexpressing IL-10.

    Science.gov (United States)

    Del Río, Laura; Murcia, Antonio; Buendía, Antonio J; Álvarez, Daniel; Ortega, Nieves; Navarro, José A; Salinas, Jesús; Caro, María Rosa

    2018-01-01

    Chlamydia abortus, like other members of the family Chlamydiaceae, have a unique intracellular developmental cycle that is characterized by its chronic nature. Infection of a flock can remain undetected for months, until abortion occurs the following reproductive season but, to date, neither the location nor the mechanisms that maintain this latent phase are fully understood. Studies have shown that IL-10 produced as a response to certain micro-organisms sustains the intracellular survival of pathogens and increases host susceptibility to chlamydial infections. In order to induce a sustained infection C. abortus, transgenic mice that constitutively express IL-10 were infected and the immunological mechanisms that maintain infection in these mice were compared with the mechanisms of a resistant wild-type mouse strain. Viable bacteria could be detected in different tissues of transgenic mice up to 28 days after infection, as analysed by bacterial isolation and immunohistochemistry. Chronic infection in these mice was associated with an impaired recruitment of macrophages, decreased iNOS activity at the site of infection and a more diffuse distribution of inflammatory cells in the liver. This murine model can be of great help for understanding the immunological and bacterial mechanisms that lead to chronic chlamydial infections. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Mathematical Modeling of Vibrio vulnificus Infection in Korea and the Influence of Global Warming.

    Science.gov (United States)

    Chu, Chaeshin; Do, Younghae; Kim, Yongkuk; Saito, Yasuhisa; Lee, Sun-Dong; Park, Haemo; Lee, Jong-Koo

    2011-06-01

    To investigate the possible link between Vibrio vulnificus population size in seawater and water temperature. We collected incidence and water temperature data in coastal regions of Korea and constructed a mathematical model that consisted of three classes; susceptible fish, infected fish available to humans, and infected humans. We developed a mathematical model to connect V. vulnificus incidence with water temperature using estimated bacterial population sizes and actual coastal water temperatures. Increased V. vulnificus population sizes in marine environments may increase the risk of infection in people who eat at coastal restaurants in Korea. Furthermore, we estimated the near-future number of infected patients using our model, which will help to establish a public-health policy to reduce the disease burden.

  19. Activity of nucleic acid polymers in rodent models of HBV infection.

    Science.gov (United States)

    Schöneweis, Katrin; Motter, Neil; Roppert, Pia L; Lu, Mengji; Wang, Baoju; Roehl, Ingo; Glebe, Dieter; Yang, Dongliang; Morrey, John D; Roggendorf, Michael; Vaillant, Andrew

    2018-01-01

    Nucleic acid polymers (NAPs) block the release of HBsAg from infected hepatocytes. These compounds have been previously shown to have the unique ability to eliminate serum surface antigen in DHBV-infected Pekin ducks and achieve multilog reduction of HBsAg or HBsAg loss in patients with chronic HBV infection and HBV/HDV coinfection. In ducks and humans, the blockage of HBsAg release by NAPs occurs by the selective targeting of the assembly and/or secretion of subviral particles (SVPs). The clinically active NAP species REP 2055 and REP 2139 were investigated in other relevant animal models of HBV infection including woodchucks chronically infected with WHV, HBV transgenic mice and HBV infected SCID-Hu mice. The liver accumulation of REP 2139 in woodchucks following subcutaneous administration was examined and was found to be similar to that observed in mice and ducks. However, in woodchucks, NAP treatment was associated with only mild (36-79% relative to baseline) reductions in WHsAg (4/10 animals) after 3-5 weeks of treatment without changes in serum WHV DNA. In HBV infected SCID-Hu mice, REP 2055 treatment was not associated with any reduction of HBsAg, HBeAg or HBV DNA in the serum after 28 days of treatment. In HBV transgenic mice, no reductions in serum HBsAg were observed with REP 2139 with up to 12 weeks of treatment. In conclusion, the antiviral effects of NAPs in DHBV infected ducks and patients with chronic HBV infection were weak or absent in woodchuck and mouse models despite similar liver accumulation of NAPs in all these species, suggesting that the mechanisms of SVP assembly and or secretion present in rodent models differs from that in DHBV and chronic HBV infections. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Prospective differentiation of clinically difficult to distinguish nodular basal cell carcinomas and intradermal nevi by non-invasive Reflectance Confocal Microscopy: a case series study

    NARCIS (Netherlands)

    Hoogedoorn, L.; Peppelman, M.; Blokx, W.A.M.; Erp, P.E.J. van; Gerritsen, M.J.P.

    2015-01-01

    BACKGROUND: Clinical differentiation between a nodular basal cell carcinoma (nBCC) and a benign intradermal nevus can be difficult. Even with additional dermoscopic evaluation, a correct diagnosis may be difficult. Currently, histopathological examination of a biopsy is the gold standard to

  1. Regression models for interval censored survival data: Application to HIV infection in Danish homosexual men

    DEFF Research Database (Denmark)

    Carstensen, Bendix

    1996-01-01

    This paper shows how to fit excess and relative risk regression models to interval censored survival data, and how to implement the models in standard statistical software. The methods developed are used for the analysis of HIV infection rates in a cohort of Danish homosexual men.......This paper shows how to fit excess and relative risk regression models to interval censored survival data, and how to implement the models in standard statistical software. The methods developed are used for the analysis of HIV infection rates in a cohort of Danish homosexual men....

  2. Hematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus [corrected].

    Directory of Open Access Journals (Sweden)

    Thomas R Shelite

    2014-07-01

    Full Text Available Orientia tsutsugamushi, the etiologic agent of scrub typhus, is a mite-borne rickettsia transmitted by the parasitic larval stage of trombiculid mites. Approximately one-third of the world's population is at risk of infection with Orientia tsutsugamushi, emphasizing its importance in global health. In order to study scrub typhus, Orientia tsutsugamushi Karp strain has been used extensively in mouse studies with various inoculation strategies and little success in inducing disease progression similar to that of human scrub typhus. The objective of this project was to develop a disease model with pathology and target cells similar to those of severe human scrub typhus. This study reports an intravenous infection model of scrub typhus in C57BL/6 mice. This mouse strain was susceptible to intravenous challenge, and lethal infection occurred after intravenous inoculation of 1.25 × 10(6 focus (FFU forming units. Signs of illness in lethally infected mice appeared on day 6 with death occurring ∼ 6 days later. Immunohistochemical staining for Orientia antigens demonstrated extensive endothelial infection, most notably in the lungs and brain. Histopathological analysis revealed cerebral perivascular, lymphohistiocytic infiltrates, focal hemorrhages, meningoencephalitis, and interstitial pneumonia. Disseminated infection of endothelial cells with Orientia in C57BL/6 mice resulted in pathology resembling that of human scrub typhus. The use of this model will allow detailed characterization of the mechanisms of immunity to and pathogenesis of O. tsutsugamushi infection.

  3. Low Dose BCG Infection as a Model for Macrophage Activation Maintaining Cell Viability

    Directory of Open Access Journals (Sweden)

    Leslie Chávez-Galán

    2016-01-01

    Full Text Available Mycobacterium bovis BCG, the current vaccine against tuberculosis, is ingested by macrophages promoting the development of effector functions including cell death and microbicidal mechanisms. Despite accumulating reports on M. tuberculosis, mechanisms of BCG/macrophage interaction remain relatively undefined. In vivo, few bacilli are sufficient to establish a mycobacterial infection; however, in vitro studies systematically use high mycobacterium doses. In this study, we analyze macrophage/BCG interactions and microenvironment upon infection with low BCG doses and propose an in vitro model to study cell activation without affecting viability. We show that RAW macrophages infected with BCG at MOI 1 activated higher and sustained levels of proinflammatory cytokines and transcription factors while MOI 0.1 was more efficient for early stimulation of IL-1β, MCP-1, and KC. Both BCG infection doses induced iNOS and NO in a dose-dependent manner and maintained nuclear and mitochondrial structures. Microenvironment generated by MOI 1 induced macrophage proliferation but not MOI 0.1 infection. In conclusion, BCG infection at low dose is an efficient in vitro model to study macrophage/BCG interactions that maintains macrophage viability and mitochondrial structures. This represents a novel model that can be applied to BCG research fields including mycobacterial infections, cancer immunotherapy, and prevention of autoimmunity and allergies.

  4. Metabolite cross-feeding enhances virulence in a model polymicrobial infection.

    Directory of Open Access Journals (Sweden)

    Matthew M Ramsey

    2011-03-01

    Full Text Available Microbes within polymicrobial infections often display synergistic interactions resulting in enhanced pathogenesis; however, the molecular mechanisms governing these interactions are not well understood. Development of model systems that allow detailed mechanistic studies of polymicrobial synergy is a critical step towards a comprehensive understanding of these infections in vivo. In this study, we used a model polymicrobial infection including the opportunistic pathogen Aggregatibacter actinomycetemcomitans and the commensal Streptococcus gordonii to examine the importance of metabolite cross-feeding for establishing co-culture infections. Our results reveal that co-culture with S. gordonii enhances the pathogenesis of A. actinomycetemcomitans in a murine abscess model of infection. Interestingly, the ability of A. actinomycetemcomitans to utilize L-lactate as an energy source is essential for these co-culture benefits. Surprisingly, inactivation of L-lactate catabolism had no impact on mono-culture growth in vitro and in vivo suggesting that A. actinomycetemcomitans L-lactate catabolism is only critical for establishing co-culture infections. These results demonstrate that metabolite cross-feeding is critical for A. actinomycetemcomitans to persist in a polymicrobial infection with S. gordonii supporting the idea that the metabolic properties of commensal bacteria alter the course of pathogenesis in polymicrobial communities.

  5. Diabetic mouse model of orthopaedic implant-related Staphylococcus aureus infection.

    Science.gov (United States)

    Lovati, Arianna B; Drago, Lorenzo; Monti, Lorenzo; De Vecchi, Elena; Previdi, Sara; Banfi, Giuseppe; Romanò, Carlo L

    2013-01-01

    Periprosthetic bacterial infections represent one of the most challenging orthopaedic complications that often require implant removal and surgical debridement and carry high social and economical costs. Diabetes is one of the most relevant risk factors of implant-related infection and its clinical occurrence is growing worldwide. The aim of the present study was to test a model of implant-related infection in the diabetic mouse, with a view to allow further investigation on the relative efficacy of prevention and treatment options in diabetic and non-diabetic individuals. A cohort of diabetic NOD/ShiLtJ mice was compared with non-diabetic CD1 mice as an in vivo model of S. aureus orthopaedic infection of bone and soft tissues after femur intramedullary pin implantation. We tested control and infected groups with 1×10(3) colony-forming units of S. aureus ATCC 25923 strain injected in the implant site. At 4 weeks post-inoculation, host response to infection, microbial biofilm formation, and bone damage were assessed by traditional diagnostic parameters (bacterial culture, C-reactive protein and white blood cell count), histological analysis and imaging techniques (micro computed tomography and scanning electron microscopy). Unlike the controls and the CD1 mice, all the diabetic mice challenged with a single inoculum of S. aureus displayed severe osteomyelitic changes around the implant. Our findings demonstrate for the first time that the diabetic mouse can be successfully used in a model of orthopaedic implant-related infection. Furthermore, the same bacteria inoculum induced periprosthetic infection in all the diabetic mice but not in the controls. This animal model of implant-related infection in diabetes may be a useful tool to test in vivo treatments in diabetic and non-diabetic individuals.

  6. Diabetic mouse model of orthopaedic implant-related Staphylococcus aureus infection.

    Directory of Open Access Journals (Sweden)

    Arianna B Lovati

    Full Text Available BACKGROUND: Periprosthetic bacterial infections represent one of the most challenging orthopaedic complications that often require implant removal and surgical debridement and carry high social and economical costs. Diabetes is one of the most relevant risk factors of implant-related infection and its clinical occurrence is growing worldwide. The aim of the present study was to test a model of implant-related infection in the diabetic mouse, with a view to allow further investigation on the relative efficacy of prevention and treatment options in diabetic and non-diabetic individuals. METHODOLOGY: A cohort of diabetic NOD/ShiLtJ mice was compared with non-diabetic CD1 mice as an in vivo model of S. aureus orthopaedic infection of bone and soft tissues after femur intramedullary pin implantation. We tested control and infected groups with 1×10(3 colony-forming units of S. aureus ATCC 25923 strain injected in the implant site. At 4 weeks post-inoculation, host response to infection, microbial biofilm formation, and bone damage were assessed by traditional diagnostic parameters (bacterial culture, C-reactive protein and white blood cell count, histological analysis and imaging techniques (micro computed tomography and scanning electron microscopy. RESULTS: Unlike the controls and the CD1 mice, all the diabetic mice challenged with a single inoculum of S. aureus displayed severe osteomyelitic changes around the implant. CONCLUSIONS: Our findings demonstrate for the first time that the diabetic mouse can be successfully used in a model of orthopaedic implant-related infection. Furthermore, the same bacteria inoculum induced periprosthetic infection in all the diabetic mice but not in the controls. This animal model of implant-related infection in diabetes may be a useful tool to test in vivo treatments in diabetic and non-diabetic individuals.

  7. Impact of vaccination on 14 high-risk HPV type infections: a mathematical modelling approach.

    Directory of Open Access Journals (Sweden)

    Simopekka Vänskä

    Full Text Available The development of high-risk human papillomavirus (hrHPV infection to cervical cancer is a complicated process. We considered solely hrHPV infections, thus avoiding the confounding effects of disease progression, screening, and treatments. To analyse hrHPV epidemiology and to estimate the overall impact of vaccination against infections with hrHPVs, we developed a dynamic compartmental transmission model for single and multiple infections with 14 hrHPV types. The infection-related parameters were estimated using population-based sexual behaviour and hrHPV prevalence data from Finland. The analysis disclosed the important role of persistent infections in hrHPV epidemiology, provided further evidence for a significant natural immunity, and demonstrated the dependence of transmission probability estimates on the model structure. The model predicted that vaccinating girls at 80% coverage will result in a 55% reduction in the overall hrHPV prevalence and a higher 65% reduction in the prevalence of persistent hrHPV infections in females. In males, the reduction will be 42% in the hrHPV prevalence solely by the herd effect from the 80% coverage in girls. If such high coverage among girls is not reached, it is still possible to reduce the female hrHPV prevalence indirectly by the herd effect if also boys are included in the vaccination program. On the other hand, any herd effects in older unvaccinated cohorts were minor. Limiting the epidemiological model to infection yielded improved understanding of the hrHPV epidemiology and of mechanisms with which vaccination impacts on hrHPV infections.

  8. Impact of Vaccination on 14 High-Risk HPV Type Infections: A Mathematical Modelling Approach

    Science.gov (United States)

    Vänskä, Simopekka; Auranen, Kari; Leino, Tuija; Salo, Heini; Nieminen, Pekka; Kilpi, Terhi; Tiihonen, Petri; Apter, Dan; Lehtinen, Matti

    2013-01-01

    The development of high-risk human papillomavirus (hrHPV) infection to cervical cancer is a complicated process. We considered solely hrHPV infections, thus avoiding the confounding effects of disease progression, screening, and treatments. To analyse hrHPV epidemiology and to estimate the overall impact of vaccination against infections with hrHPVs, we developed a dynamic compartmental transmission model for single and multiple infections with 14 hrHPV types. The infection-related parameters were estimated using population-based sexual behaviour and hrHPV prevalence data from Finland. The analysis disclosed the important role of persistent infections in hrHPV epidemiology, provided further evidence for a significant natural immunity, and demonstrated the dependence of transmission probability estimates on the model structure. The model predicted that vaccinating girls at 80% coverage will result in a 55% reduction in the overall hrHPV prevalence and a higher 65% reduction in the prevalence of persistent hrHPV infections in females. In males, the reduction will be 42% in the hrHPV prevalence solely by the herd effect from the 80% coverage in girls. If such high coverage among girls is not reached, it is still possible to reduce the female hrHPV prevalence indirectly by the herd effect if also boys are included in the vaccination program. On the other hand, any herd effects in older unvaccinated cohorts were minor. Limiting the epidemiological model to infection yielded improved understanding of the hrHPV epidemiology and of mechanisms with which vaccination impacts on hrHPV infections. PMID:24009669

  9. Resurgence of HIV infection among men who have sex with men in Switzerland: mathematical modelling study.

    Directory of Open Access Journals (Sweden)

    Ard van Sighem

    Full Text Available New HIV infections in men who have sex with men (MSM have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART. The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis.The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6% of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4% of new HIV infections. The transmission rate was at its lowest from 1995-1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate.The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions.

  10. Evaluation of genetically inactivated alpha toxin for protection in multiple mouse models of Staphylococcus aureus infection.

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    Rebecca A Brady

    Full Text Available Staphylococcus aureus is a major human pathogen and a leading cause of nosocomial and community-acquired infections. Development of a vaccine against this pathogen is an important goal. While S. aureus protective antigens have been identified in the literature, the majority have only been tested in a single animal model of disease. We wished to evaluate the ability of one S. aureus vaccine antigen to protect in multiple mouse models, thus assessing whether protection in one model translates to protection in other models encompassing the full breadth of infections the pathogen can cause. We chose to focus on genetically inactivated alpha toxin mutant HlaH35L. We evaluated the protection afforded by this antigen in three models of infection using the same vaccine dose, regimen, route of immunization, adjuvant, and challenge strain. When mice were immunized with HlaH35L and challenged via a skin and soft tissue infection model, HlaH35L immunization led to a less severe infection and decreased S. aureus levels at the challenge site when compared to controls. Challenge of HlaH35L-immunized mice using a systemic infection model resulted in a limited, but statistically significant decrease in bacterial colonization as compared to that observed with control mice. In contrast, in a prosthetic implant model of chronic biofilm infection, there was no significant difference in bacterial levels when compared to controls. These results demonstrate that vaccines may confer protection against one form of S. aureus disease without conferring protection against other disease presentations and thus underscore a significant challenge in S. aureus vaccine development.

  11. Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans

    DEFF Research Database (Denmark)

    Gottrup, Hanne; Hansen, Peter Orm; Arendt-Nielsen, Lars

    2000-01-01

    We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments....... Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following...... were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced...

  12. Pharmacokinetic modeling of gentamicin in treatment of infective endocarditis: Model development and validation of existing models.

    Directory of Open Access Journals (Sweden)

    Anna Gomes

    Full Text Available Gentamicin shows large variations in half-life and volume of distribution (Vd within and between individuals. Thus, monitoring and accurately predicting serum levels are required to optimize effectiveness and minimize toxicity. Currently, two population pharmacokinetic models are applied for predicting gentamicin doses in adults. For endocarditis patients the optimal model is unknown. We aimed at: 1 creating an optimal model for endocarditis patients; and 2 assessing whether the endocarditis and existing models can accurately predict serum levels. We performed a retrospective observational two-cohort study: one cohort to parameterize the endocarditis model by iterative two-stage Bayesian analysis, and a second cohort to validate and compare all three models. The Akaike Information Criterion and the weighted sum of squares of the residuals divided by the degrees of freedom were used to select the endocarditis model. Median Prediction Error (MDPE and Median Absolute Prediction Error (MDAPE were used to test all models with the validation dataset. We built the endocarditis model based on data from the modeling cohort (65 patients with a fixed 0.277 L/h/70kg metabolic clearance, 0.698 (±0.358 renal clearance as fraction of creatinine clearance, and Vd 0.312 (±0.076 L/kg corrected lean body mass. External validation with data from 14 validation cohort patients showed a similar predictive power of the endocarditis model (MDPE -1.77%, MDAPE 4.68% as compared to the intensive-care (MDPE -1.33%, MDAPE 4.37% and standard (MDPE -0.90%, MDAPE 4.82% models. All models acceptably predicted pharmacokinetic parameters for gentamicin in endocarditis patients. However, these patients appear to have an increased Vd, similar to intensive care patients. Vd mainly determines the height of peak serum levels, which in turn correlate with bactericidal activity. In order to maintain simplicity, we advise to use the existing intensive-care model in clinical practice to

  13. High-throughput screen for novel antimicrobials using a whole animal infection model.

    Science.gov (United States)

    Moy, Terence I; Conery, Annie L; Larkins-Ford, Jonah; Wu, Gang; Mazitschek, Ralph; Casadei, Gabriele; Lewis, Kim; Carpenter, Anne E; Ausubel, Frederick M

    2009-07-17

    The nematode Caenorhabditis elegans is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C. elegans can be infected with a broad range of human pathogens, including Enterococcus faecalis, an important human nosocomial pathogen. Here, we describe an automated, high-throughput screen of 37,200 compounds and natural product extracts for those that enhance survival of C. elegans infected with E. faecalis. Using a robot to dispense live, infected animals into 384-well plates and automated microscopy and image analysis, we identified 28 compounds and extracts not previously reported to have antimicrobial properties, including six structural classes that cure infected C. elegans animals but do not affect the growth of the pathogen in vitro, thus acting by a mechanism of action distinct from antibiotics currently in clinical use.

  14. Use of Tetravalent Galabiose for Inhibition of Streptococcus Suis Serotype 2 Infection in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Karen A. Krogfelt

    2013-04-01

    Full Text Available Streptococcus suis is an important swine pathogen associated with a variety of infections such as meningitis, arthritis and septicemia. The bacterium is zoonotic and has been found to cause meningitis especially in humans occupationally exposed to infected pigs. Since adhesion is a prerequisite for colonization and subsequent infection, anti-adhesion treatment seems a natural alternative to traditional treatment with antibiotics. In order to optimize the inhibitory potency a multivalency approach was taken in the inhibitor design. A synthetic tetravalent galabiose compound was chosen which had previously shown promising anti-adhesion effects with S. suis in vitro. The aim of this study was to evaluate the in vivo effects of the compound using an infection peritonitis mouse model. As such S. suis serotype 2 infection and treatment were tested in vivo and the effects were compared to the effect of treatment with penicillin.

  15. Prevalence of local immune response against oral infection in a Drosophila/Pseudomonas infection model.

    Directory of Open Access Journals (Sweden)

    Peter Liehl

    2006-06-01

    Full Text Available Pathogens have developed multiple strategies that allow them to exploit host resources and resist the immune response. To study how Drosophila flies deal with infectious diseases in a natural context, we investigated the interactions between Drosophila and a newly identified entomopathogen, Pseudomonas entomophila. Flies orally infected with P. entomophila rapidly succumb despite the induction of both local and systemic immune responses, indicating that this bacterium has developed specific strategies to escape the fly immune response. Using a combined genetic approach on both host and pathogen, we showed that P. entomophila virulence is multi-factorial with a clear differentiation between factors that trigger the immune response and those that promote pathogenicity. We demonstrate that AprA, an abundant secreted metalloprotease produced by P. entomophila, is an important virulence factor. Inactivation of aprA attenuated both the capacity to persist in the host and pathogenicity. Interestingly, aprA mutants were able to survive to wild-type levels in immune-deficient Relish flies, indicating that the protease plays an important role in protection against the Drosophila immune response. Our study also reveals that the major contribution to the fly defense against P. entomophila is provided by the local, rather than the systemic immune response. More precisely, our data points to an important role for the antimicrobial peptide Diptericin against orally infectious Gram-negative bacteria, emphasizing the critical role of local antimicrobial peptide expression against food-borne pathogens.

  16. Validation of the cephalosporin intradermal skin test for predicting immediate hypersensitivity: a prospective study with drug challenge.

    Science.gov (United States)

    Yoon, S-Y; Park, S Y; Kim, S; Lee, T; Lee, Y S; Kwon, H-S; Cho, Y S; Moon, H-B; Kim, T-B

    2013-07-01

    Cephalosporin is a major offending agent in terms of drug hypersensitivity along with penicillin. Cephalosporin intradermal skin tests (IDTs) have been widely used; however, their validity for predicting immediate hypersensitivity has not been studied. This study aimed to determine the predictive value of cephalosporin intradermal skin testing before administration of the drug. We prospectively conducted IDTs with four cephalosporins, one each of selected first-, second-, third-, or fourth-generation cephalosporins: ceftezol; cefotetan or cefamandole; ceftriaxone or cefotaxime; and flomoxef, respectively, as well as with penicillin G. After the skin test, whatever the result, one of the tested cephalosporins was administered intravenously and the patient was carefully observed. We recruited 1421 patients who required preoperative cephalosporins. Seventy-four patients (74/1421, 5.2%) were positive to at least one cephalosporin. However, none of responders had immediate hypersensitivity reactions after a challenge dose of the same or different cephalosporin, which were positive in the skin test. Four patients who suffered generalized urticaria and itching after challenge gave negative skin tests for the corresponding drug. The IDT for cephalosporin had a sensitivity of 0%, a specificity of 97.5%, a negative predictive value of 99.7%, and a positive predictive value (PPV) of 0%, when challenged with the same drugs that were positive in the skin test. Routine skin testing with a cephalosporin before its administration is not useful for predicting immediate hypersensitivity because of the extremely low sensitivity and PPV of the skin test (CRIS registration no. KCT0000455). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Intradermal administration of endothelin-1 attenuates endothelium-dependent and -independent cutaneous vasodilation via Rho kinase in young adults.

    Science.gov (United States)

    Fujii, Naoto; Amano, Tatsuro; Halili, Lyra; Louie, Jeffrey C; Zhang, Sarah Y; McNeely, Brendan D; Kenny, Glen P

    2017-01-01

    We recently showed that intradermal administration of endothelin-1 diminished endothelium-dependent and -independent cutaneous vasodilation. We evaluated the hypothesis that Rho kinase may be a mediator of this response. We also sought to evaluate if endothelin-1 increases sweating. In 12 adults (25 ± 6 yr), we measured cutaneous vascular conductance (CVC) and sweating during 1) endothelium-dependent vasodilation induced via administration of incremental doses of methacholine (0.25, 5, 100, and 2,000 mM each for 25 min) and 2) endothelium-independent vasodilation induced via administration of 50 mM sodium nitroprusside (20-25 min). Responses were evaluated at four skin sites treated with either 1) lactated Ringer solution (Control), 2) 400 nM endothelin-1, 3) 3 mM HA-1077 (Rho kinase inhibitor), or 4) endothelin-1+HA-1077. Pharmacological agents were intradermally administered via microdialysis. Relative to the Control site, endothelin-1 attenuated endothelium-dependent vasodilation (CVC at 2,000 mM methacholine, 80 ± 10 vs. 56 ± 15%max, P 0.05). Endothelium-independent vasodilation was attenuated by endothelin-1 compared with the Control site (CVC, 92 ± 13 vs. 70 ± 14%max, P 0.05). There was no between-site difference in sweating throughout (P > 0.05). We show that in young adults, Rho kinase is an important mediator of the endothelin-1-mediated attenuation of endothelium-dependent and -independent cutaneous vasodilation, and that endothelin-1 does not increase sweating. Copyright © 2017 the American Physiological Society.

  18. Comparison of IgE test results with intradermal skin tests for dust mites and storage mites in atopic dogs.

    Science.gov (United States)

    Popiel, J; Cekiera, A

    2015-01-01

    Atopic dermatitis is one of the most frequent allergic diseases in dogs. There are many methods of treating its symptoms but specific immunotherapy has recently gained high popularity. Before the application of specific immunotherapy, it is necessary to identify the allergens provoking the reaction of hypersensitivity in the selected animal. This raises a question about the method of allergen identification the medical practitioner decides to use in order to obtain the most credible result. The authors of the present study decided to compare the results of intradermal allergic tests and the results of an IgE screening test carried out using the FcɛRIα receptor method. The aim of the study was to compare the results of both tests directed to dust and storage mites. The study proves that in case of the IgE screening tests (for a group of allergens), the sensitivity is quite high (85 to 90.69%) but the specificity of these tests is insufficient (25 to 50%). In case of antibodies for the selected mites the sensitivity and specificity was too low (65.1 to 89.4% for the sensitivity, with only 14.2 to 33.3% for the specificity). Only in case of D. petronyssinus the results were higher with the sensitivity calculated at 65.1% and the specificity at 80%. The IgE screening test carried out using the FcɛRIα receptor method is reliable only in case of screening test for mites and the intradermal allergic test remains the gold standard for allergy testing.

  19. A Study on the Alterations in Skin Viscoelasticity before and after an Intradermal Administration of Growth Factor

    Science.gov (United States)

    Ono, Ichiro

    2011-01-01

    Background: While photo-aging is believed to be preventable by the complete blockage of ultraviolet rays, there is no epoch-making method except sing fillers or autologous fat injection, for rejuvenating the skin once it has aged. Objective: Our group developed a new method for rejuvenating aged skin by the direct intradermal injection of basic fibroblast growth factor, the first method of its kind in the world. In this paper we report the results of long-term follow-up observations and alterations in skin viscoelasticity before and after this treatment. Materials and Methods: A single dose of growth factor was injected directly into aged skin of the dorsal surface of the hand intradermally. The skin viscoelasticity of 50 treated cases was measured by a cutometer just before the treatment and at 1, 3, 6, and 9 months after treatment, respectively. Results: We observed the following rejuvenating effects: improved skin softness, gradual improvement of turgor, improved thickness of atrophied skin, and greatly improved viscoelasticity which reveals the improvement of biomechanical properties of the treated aged skin. According to the comparisons of viscoelasticity between pre- and post-treatment, the rejuvenated changes of R2 and R7 values were comparable to an age difference of more than 20 years. Conclusion: This method was confirmed to have excellent effects in rejuvenating aged skin safely and reliably including biomechanical properties. With this advance, we expect conventional non-physiological skin rejuvenating treatments to be replaced by a much more fundamental method using one-time injections of the growth factor. PMID:21976900

  20. Development of an Innovative Intradermal siRNA Delivery System Using a Combination of a Functional Stearylated Cytoplasm-Responsive Peptide and a Tight Junction-Opening Peptide

    Directory of Open Access Journals (Sweden)

    Hisako Ibaraki

    2016-09-01

    Full Text Available As a new category of therapeutics for skin diseases including atopic dermatitis (AD, nucleic acids are gaining importance in the clinical setting. Intradermal administration is noninvasive and improves patients′ quality of life. However, intradermal small interfering RNA (siRNA delivery is difficult because of two barriers encountered in the skin: intercellular lipids in the stratum corneum and tight junctions in the stratum granulosum. Tight junctions are the major barrier in AD; therefore, we focused on functional peptides to devise an intradermal siRNA delivery system for topical skin application. In this study, we examined intradermal siRNA permeability in the tape-stripped (20 times back skin of mice or AD-like skin of auricles treated with 6-carboxyfluorescein-aminohexyl phosphoramidite (FAM-labeled siRNA, the tight junction modulator AT1002, and the functional cytoplasm-responsive stearylated peptide STR-CH2R4H2C by using confocal laser microscopy. We found that strong fluorescence was observed deep and wide in the epidermis and dermis of back skin and AD-like ears after siRNA with STR-CH2R4H2C and AT1002 treatment. After 10 h from administration, brightness of FAM-siRNA was significantly higher for STR-CH2R4H2C + AT1002, compared to other groups. In addition, we confirmed the nontoxicity of STR-CH2R4H2C as a siRNA carrier using PAM212 cells. Thus, our results demonstrate the applicability of the combination of STR-CH2R4H2C and AT1002 for effective intradermal siRNA delivery.

  1. Optimization of an infected shoe model for the evaluation of an ultraviolet shoe sanitizer device.

    Science.gov (United States)

    Ghannoum, Mahmoud A; Isham, Nancy; Long, Lisa

    2012-01-01

    Onychomycosis and tinea pedis (athlete's foot) are infections of the nails and skin caused by pathogenic fungi collectively known as dermatophytes. These infections are difficult to treat, and patients often relapse; it is thought that a patient's footwear becomes infected with these fungal organisms and, thus, is an important reservoir for reinfection. Therefore, it is important to find an effective means for killing the dermatophytes that may have colonized the inner surface of the shoes of patients with superficial fungal infections. In this study, we developed an in vitro model for culturing dermatophytes in footwear and used this model to evaluate the effectiveness of a commercial ultraviolet shoe sanitizer in eradicating the fungal elements residing in shoes. Leather and athletic shoes (24 pairs) were inoculated with either Trichophyton rubrum or Trichophyton mentagrophytes (10(7) colony-forming units/mL) strains and were placed at 35°C for 4 to 5 days. Next, we compared the ability of swabbing versus scraping to collect microorganisms from infected shoes. Following the optimized method, shoes were infected and were irradiated with one to three cycles of radiation. The inner surfaces of the shoes were swabbed or scraped, and the specimens were cultured for dermatophyte colony-forming units. Leather and canvas shoes were infected to the same extent. Moreover, scraping with a scalpel was overall more effective than was swabbing with a cotton-tipped applicator in recovering viable fungal elements. Irradiation of shoes with one, two, or three cycles resulted in reduction of fungal colonization to the same extent. The developed infected shoe model is useful for assessing the effectiveness of ultraviolet shoe sanitizers. Also, ultraviolet treatment of shoes with a commercial ultraviolet C sanitizing device was effective in reducing the fungal burden in shoes. These findings have implications regarding breaking foot infection cycles.

  2. Field application of immunoassays for the detection of Mycobacterium bovis infection in the African buffalo (Syncerus caffer)

    NARCIS (Netherlands)

    van der Heijden, E.M.D.L.; Jenkins, A.; Cooper, D.; Rutten, V.P.M.G.; Michel, A.L.

    2016-01-01

    The African buffalo (Syncerus caffer) is considered the most important maintenance host of bovine tuberculosis (BTB) in wildlife in Southern Africa. The diagnosis of Mycobacterium bovis infection in this species mostly relies on the single intradermal comparative tuberculin test (SICTT). As an

  3. Virulence of invasive Salmonella Typhimurium ST313 in animal models of infection.

    Directory of Open Access Journals (Sweden)

    Girish Ramachandran

    2017-08-01

    Full Text Available Salmonella Typhimurium sequence type (ST 313 produces septicemia in infants in sub-Saharan Africa. Although there are known genetic and phenotypic differences between ST313 strains and gastroenteritis-associated ST19 strains, conflicting data about the in vivo virulence of ST313 strains have been reported. To resolve these differences, we tested clinical Salmonella Typhimurium ST313 and ST19 strains in murine and rhesus macaque infection models. The 50% lethal dose (LD50 was determined for three Salmonella Typhimurium ST19 and ST313 strains in mice. For dissemination studies, bacterial burden in organs was determined at various time-points post-challenge. Indian rhesus macaques were infected with one ST19 and one ST313 strain. Animals were monitored for clinical signs and bacterial burden and pathology were determined. The LD50 values for ST19 and ST313 infected mice were not significantly different. However, ST313-infected BALB/c mice had significantly higher bacterial numbers in blood at 24 h than ST19-infected mice. ST19-infected rhesus macaques exhibited moderate-to-severe diarrhea while ST313-infected monkeys showed no-to-mild diarrhea. ST19-infected monkeys had higher bacterial burden and increased inflammation in tissues. Our data suggest that Salmonella Typhimurium ST313 invasiveness may be investigated using mice. The non-human primate results are consistent with clinical data, suggesting that ST313 strains do not cause diarrhea.

  4. Revisiting a two-patch SIS model with infection during transport.

    Science.gov (United States)

    Arino, Julien; Sun, Chengjun; Yang, Wei

    2016-03-01

    We incorporate parameter heterogeneity in a two-patch susceptible-infectious-susceptible (SIS) epidemic model with infection during transport and prove that the disease-free and endemic equilibria are globally asymptotically stable when the basic reproduction number [Formula: see text] and [Formula: see text], respectively. We find that infection during transport increases the possibility that the disease persists in both patches and amplifies prevalence when disease is present. We then study the effect of a perfect unilateral exit screening programme. Finally, we compare numerically the effects of using different incidence functions for infection within and while travelling between patches, and find that using mass action incidence to model infection during transport has the effect of maintaining disease prevalence at a higher level compared with when standard incidence is used. © The Authors 2015. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  5. The Red Flour Beetle as a Model for Bacterial Oral Infections

    Science.gov (United States)

    Milutinović, Barbara; Stolpe, Clemens; Peuβ, Robert; Armitage, Sophie A. O.; Kurtz, Joachim

    2013-01-01

    Experimental infection systems are important for studying antagonistic interactions and coevolution between hosts and their pathogens. The red flour beetle Tribolium castaneum and the spore-forming bacterial insect pathogen Bacillus thuringiensis (Bt) are widely used and tractable model organisms. However, they have not been employed yet as an efficient experimental system to study host-pathogen interactions. We used a high throughput oral infection protocol to infect T. castaneum insects with coleopteran specific B. thuringiensis bv. tenebrionis (Btt) bacteria. We found that larval mortality depends on the dietary spore concentration and on the duration of exposure to the spores. Furthermore, differential susceptibility of larvae from different T. castaneum populations indicates that the host genetic background influences infection success. The recovery of high numbers of infectious spores from the cadavers indicates successful replication of bacteria in the host and suggests that Btt could establish infectious cycles in T. castaneum in nature. We were able to transfer plasmids from Btt to a non-pathogenic but genetically well-characterised Bt strain, which was thereafter able to successfully infect T. castaneum, suggesting that factors residing on the plasmids are important for the virulence of Btt. The availability of a genetically accessible strain will provide an ideal model for more in-depth analyses of pathogenicity factors during oral infections. Combined with the availability of the full genome sequence of T. castaneum, this system will enable analyses of host responses during infection, as well as addressing basic questions concerning host-parasite coevolution. PMID:23737991

  6. The red flour beetle as a model for bacterial oral infections.

    Directory of Open Access Journals (Sweden)

    Barbara Milutinović

    Full Text Available Experimental infection systems are important for studying antagonistic interactions and coevolution between hosts and their pathogens. The red flour beetle Tribolium castaneum and the spore-forming bacterial insect pathogen Bacillus thuringiensis (Bt are widely used and tractable model organisms. However, they have not been employed yet as an efficient experimental system to study host-pathogen interactions. We used a high throughput oral infection protocol to infect T. castaneum insects with coleopteran specific B. thuringiensis bv. tenebrionis (Btt bacteria. We found that larval mortality depends on the dietary spore concentration and on the duration of exposure to the spores. Furthermore, differential susceptibility of larvae from different T. castaneum populations indicates that the host genetic background influences infection success. The recovery of high numbers of infectious spores from the cadavers indicates successful replication of bacteria in the host and suggests that Btt could establish infectious cycles in T. castaneum in nature. We were able to transfer plasmids from Btt to a non-pathogenic but genetically well-characterised Bt strain, which was thereafter able to successfully infect T. castaneum, suggesting that factors residing on the plasmids are important for the virulence of Btt. The availability of a genetically accessible strain will provide an ideal model for more in-depth analyses of pathogenicity factors during oral infections. Combined with the availability of the full genome sequence of T. castaneum, this system will enable analyses of host responses during infection, as well as addressing basic questions concerning host-parasite coevolution.

  7. Ultrastructural study on experimental infection of rotavirus in a murine heterologous model

    Directory of Open Access Journals (Sweden)

    Selma Majerowicz

    1994-09-01

    Full Text Available Viral replication, histopathological and ultrastructural changes were observed for a period of nine days in the small intestine of suckling mice infected with a simian rotavirus (SA11. Samples taken from duodenum, jejunun and ileum were prepared for light microscopy, transmission and scanning electron microscopy analysis. Histopathologic effect could be detected within 8 hr post-infection, when only a few altered cells were observed. Damage was extensive after 16 hr post-infection, showing swollen enterocytes and reduced and irregularly oriented microvilli at intestinal villi tips. Virus particles were detected at 16 and 48 hr post-infection, budding from the viroplasm into the rough endoplasmic reticulum cisternae in ileum enterocytes. Clear evidence of viral replication, observed by electron microscopy was not described before in heterologous murine models. Regeneration of the intestinal villi began at the third day post-infection. Despite some differences observed in clinical symptoms and microscopic analysis of homologous and heterologous rotavirus infections, we concluded that mechanisms of heterologous rotavirus infection in mice follow similar patterns to those observed in the homologous models.

  8. Cell Culture Models for the Investigation of Hepatitis B and D Virus Infection.

    Science.gov (United States)

    Verrier, Eloi R; Colpitts, Che C; Schuster, Catherine; Zeisel, Mirjam B; Baumert, Thomas F

    2016-09-20

    Chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) infections are major causes of liver disease and hepatocellular carcinoma worldwide. Despite the presence of an efficient preventive vaccine, more than 250 million patients are chronically infected with HBV. Current antivirals effectively control but only rarely cure chronic infection. While the molecular biology of the two viruses has been characterized in great detail, the absence of robust cell culture models for HBV and/or HDV infection has limited the investigation of virus-host interactions. Native hepatoma cell lines do not allow viral infection, and the culture of primary hepatocytes, the natural host cell for the viruses, implies a series of constraints restricting the possibilities of analyzing virus-host interactions. Recently, the discovery of the sodium taurocholate co-transporting polypeptide (NTCP) as a key HBV/HDV cell entry factor has opened the door to a new era of investigation, as NTCP-overexpressing hepatoma cells acquire susceptibility to HBV and HDV infections. In this review, we summarize the major cell culture models for HBV and HDV infection, discuss their advantages and limitations and highlight perspectives for future developments.

  9. Cell Culture Models for the Investigation of Hepatitis B and D Virus Infection

    Directory of Open Access Journals (Sweden)

    Eloi R. Verrier

    2016-09-01

    Full Text Available Chronic hepatitis B virus (HBV and hepatitis D virus (HDV infections are major causes of liver disease and hepatocellular carcinoma worldwide. Despite the presence of an efficient preventive vaccine, more than 250 million patients are chronically infected with HBV. Current antivirals effectively control but only rarely cure chronic infection. While the molecular biology of the two viruses has been characterized in great detail, the absence of robust cell culture models for HBV and/or HDV infection has limited the investigation of virus-host interactions. Native hepatoma cell lines do not allow viral infection, and the culture of primary hepatocytes, the natural host cell for the viruses, implies a series of constraints restricting the possibilities of analyzing virus-host interactions. Recently, the discovery of the sodium taurocholate co-transporting polypeptide (NTCP as a key HBV/HDV cell entry factor has opened the door to a new era of investigation, as NTCP-overexpressing hepatoma cells acquire susceptibility to HBV and HDV infections. In this review, we summarize the major cell culture models for HBV and HDV infection, discuss their advantages and limitations and highlight perspectives for future developments.

  10. Asymptotic behavior of a stochastic delayed HIV-1 infection model with nonlinear incidence

    Science.gov (United States)

    Liu, Qun; Jiang, Daqing; Hayat, Tasawar; Ahmad, Bashir

    2017-11-01

    In this paper, a stochastic delayed HIV-1 infection model with nonlinear incidence is proposed and investigated. First of all, we prove that there is a unique global positive solution as desired in any population dynamics. Then by constructing some suitable Lyapunov functions, we show that if the basic reproduction number R0 ≤ 1, then the solution of the stochastic system oscillates around the infection-free equilibrium E0, while if R0 > 1, then the solution of the stochastic system fluctuates around the infective equilibrium E∗. Sufficient conditions of these results are established. Finally, we give some examples and a series of numerical simulations to illustrate the analytical results.

  11. Specific-Pathogen-Free Pigs as an Animal Model for Studying Chlamydia trachomatis Genital Infection

    OpenAIRE

    Vanrompay, Daisy; Hoang, Thi Q. T.; De Vos, Liselotte; Verminnen, Kristel; Harkinezhad, Taher; Chiers, Koen; Morré, Servaas A.; Cox, Eric

    2005-01-01

    The purpose of the present study was to evaluate pigs as a large-animal model for female genital infection with two Chlamydia trachomatis human serovar E strains. Sixteen-week-old specific-pathogen-free female pigs (gilts) were intravaginally infected with the trachoma type E reference strain Bour or the urogenital serovar E strain 468. Several conclusions can be drawn from our findings on the pathogenicity of a primary C. trachomatis genital infection in gilts. First of all, we demonstrated ...

  12. A differential equation model of HIV infection of CD4+ T-cells with cure rate

    Science.gov (United States)

    Zhou, Xueyong; Song, Xinyu; Shi, Xiangyun

    2008-06-01

    A differential equation model of HIV infection of CD4+ T-cells with cure rate is studied. We prove that if the basic reproduction number R0HIV infection is cleared from the T-cell population and the disease dies out; if R0>1, the HIV infection persists in the host. We find that the chronic disease steady state is globally asymptotically stable if R0>1. Furthermore, we also obtain the conditions for which the system exists an orbitally asymptotically stable periodic solution. Numerical simulations are presented to illustrate the results.

  13. Borrelia persica Infection in Immunocompetent Mice--A New Tool to Study the Infection Kinetics In Vivo.

    Science.gov (United States)

    Schwarzer, Sandra; Overzier, Evelyn; Hermanns, Walter; Baneth, Gad; Straubinger, Reinhard K

    2016-02-01

    Borrelia persica, a bacterium transmitted by the soft tick Ornithodoros tholozani, causes tick-borne relapsing fever in humans in the Middle East, Central Asia and the Indian peninsula. Immunocompetent C3H/HeOuJ mice were infected intradermally with B. persica at varying doses: 1 x 10(6), 1 x 10(4), 1 x 10(2) and 4 x 10(0) spirochetes/mouse. Subsequently, blood samples were collected and screened for the presence of B. persica DNA. Spirochetes were detected in all mice infected with 1 x 10(6), 1 x 10(4) and 1 x 10(2) borrelia by real-time PCR targeting the flaB gene of the bacterium. Spirochetemia developed with a one- to two-day delay when 1 x 10(4) and 1 x 10(2) borrelia were inoculated. Mice injected with only four organisms were negative in all tests. No clinical signs were observed when infected mice were compared to negative control animals. Organs (heart, spleen, urinary bladder, tarsal joint, skin and brain) were tested for B. persica-specific DNA and cultured for the detection of viable spirochetes. Compiled data show that the target organs of B. persica infections are the brain and the skin. A newly developed serological two-tiered test system (ELISA and western blot) for the detection of murine IgM, IgG and IgA antibody titers against B. persica showed a vigorous antibody response of the mice during infection. In conclusion, the infection model described here for B. persica is a platform for in vivo studies to decipher the so far unexplored survival strategies of this Borrelia species.

  14. A privileged intraphagocyte niche is responsible for disseminated infection of Staphylococcus aureus in a zebrafish model

    Science.gov (United States)

    Prajsnar, Tomasz K; Hamilton, Ruth; Garcia-Lara, Jorge; McVicker, Gareth; Williams, Alexander; Boots, Michael; Foster, Simon J; Renshaw, Stephen A

    2012-01-01

    The innate immune system is the primary defence against the versatile pathogen, Staphylococcus aureus. How this organism is able to avoid immune killing and cause infections is poorly understood. Using an established larval zebrafish infection model, we have shown that overwhelming infection is due to subversion of phagocytes by staphylococci, allowing bacteria to evade killing and found foci of disease. Larval zebrafish coinfected with two S. aureus strains carrying different fluorescent reporter gene fusions (but otherwise isogenic) had bacterial lesions, at the time of host death, containing predominantly one strain. Quantitative data using two marked strains revealed that the strain ratios, during overwhelming infection, were often skewed towards the extremes, with one strain predominating. Infection with passaged bacterial clones revealed the phenomenon not to bedue to adventitious mutations acquired by the pathogen. After infection of the host, all bacteria are internalized by phagocytes and the skewing of population ratios is absolutely dependent on the presence of phagocytes. Mathematical modelling of pathogen population dynamics revealed the data patterns are consistent with the hypothesis that a small number of infected phagocytes serve as an intracellular reservoir for S. aureus, which upon release leads to disseminated infection. Strategies to specifically alter neutrophil/macrophage numbers were used to map the potential subpopulation of phagocytes acting as a pathogen reservoir, revealing neutrophils as the likely ‘niche’. Subsequently in a murine sepsis model, S. aureus abscesses in kidneys were also found to be predominantly clonal, therefore likely founded by an individual cell, suggesting a potential mechanism analogous to the zebrafish model with few protected niches. These findings add credence to the argument that S. aureus control regimes should recognize both the intracellular as well as extracellular facets of the S. aureus life cycle

  15. Persistence of an SEIR Model with Immigration Dependent on the Prevalence of Infection

    Directory of Open Access Journals (Sweden)

    Wenjuan Wang

    2010-01-01

    Full Text Available We incorporate the immigration of susceptible individuals into an SEIR epidemic model, assuming that the immigration rate decreases as the spread of infection increases. For this model, the basic reproduction number, R0, is found, which determines that the disease is either extinct or persistent ultimately. The obtained results show that the disease becomes extinct as R01.

  16. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens

    Science.gov (United States)

    López Hernández, Yamilé; Yero, Daniel; Pinos-Rodríguez, Juan M.; Gibert, Isidre

    2015-01-01

    Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host–pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host–pathogen interactions. PMID:25699030

  17. Development of Hamster Models for Acute and Chronic Infections with Leptospira borgpetersenii serovar Hardjo

    Science.gov (United States)

    The Golden Syrian hamster is frequently used as a small animal model to study acute leptospirosis. However, use of this small animal model to study Leptospira borgpetersenii serovar Hardjo infections has not been well documented. Cattle are the normal maintenance hosts of L. borgpetersenii serovar...

  18. Modeling the Fate of Expiratory Aerosols and the Associated Infection Risk in an Aircraft Cabin Environment

    DEFF Research Database (Denmark)

    Wan, M.P.; To, G.N.S.; Chao, C.Y.H.

    2009-01-01

    The transport and deposition of polydispersed expiratory aerosols in an aircraft cabin were simulated using a Lagrangian-based model validated by experiments conducted in an aircraft cabin mockup. Infection risk by inhalation was estimated using the aerosol dispersion data and a model was developed...

  19. ModeLang: a new approach for experts-friendly viral infections modeling.

    Science.gov (United States)

    Wasik, Szymon; Prejzendanc, Tomasz; Blazewicz, Jacek

    2013-01-01

    Computational modeling is an important element of systems biology. One of its important applications is modeling complex, dynamical, and biological systems, including viral infections. This type of modeling usually requires close cooperation between biologists and mathematicians. However, such cooperation often faces communication problems because biologists do not have sufficient knowledge to understand mathematical description of the models, and mathematicians do not have sufficient knowledge to define and verify these models. In many areas of systems biology, this problem has already been solved; however, in some of these areas there are still certain problematic aspects. The goal of the presented research was to facilitate this cooperation by designing seminatural formal language for describing viral infection models that will be easy to understand for biologists and easy to use by mathematicians and computer scientists. The ModeLang language was designed in cooperation with biologists and its computer implementation was prepared. Tests proved that it can be successfully used to describe commonly used viral infection models and then to simulate and verify them. As a result, it can make cooperation between biologists and mathematicians modeling viral infections much easier, speeding up computational verification of formulated hypotheses.

  20. Global stability for an SEI model of infectious disease with age structure and immigration of infecteds.

    Science.gov (United States)

    McCluskey, C Connell

    2016-04-01

    We study a model of disease transmission with continuous age-structure for latently infected individuals and for infectious individuals and with immigration of new individuals into the susceptible, latent and infectious classes. The model is very appropriate for tuberculosis. A Lyapunov functional is used to show that the unique endemic equilibrium is globally stable for all parameter values.

  1. Regression models for interval censored survival data: Application to HIV infection in Danish homosexual men

    DEFF Research Database (Denmark)

    Carstensen, Bendix

    1996-01-01

    This paper shows how to fit excess and relative risk regression models to interval censored survival data, and how to implement the models in standard statistical software. The methods developed are used for the analysis of HIV infection rates in a cohort of Danish homosexual men....

  2. Semi-Analytic Solution of HIV and TB Co-Infection Model | Bolarin ...

    African Journals Online (AJOL)

    In this work we developed and analyzed a mathematical model of HIV and TB coinfection. The model is a first order Ordinary Differential Equations, in which the human population is divided into six mutually- exclusive compartments namely; TB- Susceptible individuals (S), TB-Infected individuals (I), TB-Recovered ...

  3. Study of action of biological aerococcus аutosymbiont on the model of staphylococcal infection

    Directory of Open Access Journals (Sweden)

    Stepanskyi D.O.

    2017-06-01

    Full Text Available The paper presents data on the study of the antagonistic effect of aerococcus autosymbionts in experimental models of infections caused by staphylococci. To study the antagonistic action of aerococcus autosymbiont on staphylococcus, a model of chronic staphylococcal infection in white mice and rabbits was used. In staphylococcal experimental infection, aerococcus antagonistic action against staphylococcus was tested by subcutaneous injection on white mice. Aerococci survival under the skin was studied. Aerococcus autosymbionts introduced under the skin to staphylococcus in 5 hours and 3 hours after administration of the latter cause antagonist effect and inhibit the development of infiltrates. Similar results were obtained when introducing aerococcus autosymbionts in the focus of infection in 5 minutes, 5 minutes and 3 hours, 1 and 5 hours after infection. Aerococci introduced after 24 and 48 hours shortened terms of disease manifestations as compared to the control group of mice. The therapeutic effect of aerococcus autosymbionts was tested on the experimental model of burns and wounds infected with staphylococcus. In animals with wounds treated with aerococcus autostrains the number of pathogenic staphylococci was 10 times less than in the control group. According to our observations aerococcus autosymbionts showed no irritant effect when applied on the wound surface, helped its healing, sharply reduced the percentage of staphylococcus inoculation from wound secretions.

  4. Understanding Experimental LCMV Infection of Mice: The Role of Mathematical Models

    Directory of Open Access Journals (Sweden)

    Gennady Bocharov

    2015-01-01

    Full Text Available Virus infections represent complex biological systems governed by multiple-level regulatory processes of virus replication and host immune responses. Understanding of the infection means an ability to predict the systems behaviour under various conditions. Such predictions can only rely upon quantitative mathematical models. The model formulations should be tightly linked to a fundamental step called “coordinatization” (Hermann Weyl, that is, the definition of observables, parameters, and structures that enable the link with a biological phenotype. In this review, we analyse the mathematical modelling approaches to LCMV infection in mice that resulted in quantification of some fundamental parameters of the CTL-mediated virus control including the rates of T cell turnover, infected target cell elimination, and precursor frequencies. We show how the modelling approaches can be implemented to address diverse aspects of immune system functioning under normal conditions and in response to LCMV and, importantly, make quantitative predictions of the outcomes of immune system perturbations. This may highlight the notion that data-driven applications of meaningful mathematical models in infection biology remain a challenge.

  5. Models of Caenorhabditis elegans infection by bacterial and fungal pathogens.

    Science.gov (United States)

    Powell, Jennifer R; Ausubel, Frederick M

    2008-01-01

    The nematode Caenorhabditis elegans is a simple model host for studying the relationship between the animal innate immune system and a variety of bacterial and fungal pathogens. Extensive genetic and molecular tools are available in C. elegans, facilitating an in-depth analysis of host defense factors and pathogen virulence factors. Many of these factors are conserved in insects and mammals, indicating the relevance of the nematode model to the vertebrate innate immune response. Here, we describe pathogen assays for a selection of the most commonly studied bacterial and fungal pathogens using the C. elegans model system.

  6. A Novel 3D Skin Explant Model to Study Anaerobic Bacterial Infection

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    Grazieli Maboni

    2017-09-01

    Full Text Available Skin infection studies are often limited by financial and ethical constraints, and alternatives, such as monolayer cell culture, do not reflect many cellular processes limiting their application. For a more functional replacement, 3D skin culture models offer many advantages such as the maintenance of the tissue structure and the cell types present in the host environment. A 3D skin culture model can be set up using tissues acquired from surgical procedures or post slaughter, making it a cost effective and attractive alternative to animal experimentation. The majority of 3D culture models have been established for aerobic pathogens, but currently there are no models for anaerobic skin infections. Footrot is an anaerobic bacterial infection which affects the ovine interdigital skin causing a substantial animal welfare and financial impact worldwide. Dichelobacter nodosus is a Gram-negative anaerobic bacterium and the causative agent of footrot. The mechanism of infection and host immune response to D. nodosus is poorly understood. Here we present a novel 3D skin ex vivo model to study anaerobic bacterial infections using ovine skin explants infected with D. nodosus. Our results demonstrate that D. nodosus can invade the skin explant, and that altered expression of key inflammatory markers could be quantified in the culture media. The viability of explants was assessed by tissue integrity (histopathological features and cell death (DNA fragmentation over 76 h showing the model was stable for 28 h. D. nodosus was quantified in all infected skin explants by qPCR and the bacterium was visualized invading the epidermis by Fluorescent in situ Hybridization. Measurement of pro-inflammatory cytokines/chemokines in the culture media revealed that the explants released IL1β in response to bacteria. In contrast, levels of CXCL8 production were no different to mock-infected explants. The 3D skin model realistically simulates the interdigital skin and has

  7. Cytosolic caspases mediate mislocalised SOD2 depletion in an in vitro model of chronic prion infection

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    Layla Sinclair

    2013-07-01

    Oxidative stress as a contributor to neuronal death during prion infection is supported by the fact that various oxidative damage markers accumulate in the brain during the course of this disease. The normal cellular substrate of the causative agent, the prion protein, is also linked with protective functions against oxidative stress. Our previous work has found that, in chronic prion infection, an apoptotic subpopulation of cells exhibit oxidative stress and the accumulation of oxidised lipid and protein aggregates with caspase recruitment. Given the likely failure of antioxidant defence mechanisms within apoptotic prion-infected cells, we aimed to investigate the role of the crucial antioxidant pathway components, superoxide dismutases (SOD 1 and 2, in an in vitro model of chronic prion infection. Increased total SOD activity, attributable to SOD1, was found in the overall population coincident with a decrease in SOD2 protein levels. When apoptotic cells were separated from the total population, the induction of SOD activity in the infected apoptotic cells was lost, with activity reduced back to levels seen in mock-infected control cells. In addition, mitochondrial superoxide production was increased and mitochondrial numbers decreased in the infected apoptotic subpopulation. Furthermore, a pan-caspase probe colocalised with SOD2 outside of mitochondria within cytosolic aggregates in infected cells and inhibition of caspase activity was able to restore cellular levels of SOD2 in the whole unseparated infected population to those of mock-infected control cells. Our results suggest that prion propagation exacerbates an apoptotic pathway whereby mitochondrial dysfunction follows mislocalisation of SOD2 to cytosolic caspases, permitting its degradation. Eventually, cellular capacity to maintain oxidative homeostasis is overwhelmed, thus resulting in cell death.

  8. Nursing Care Model Based on Knowledge Management in Preventing Nosocomial Infection After Caesarean Section in Hospital

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    Ahsan Ahsan

    2016-09-01

    Full Text Available Introduction: Nosocomial infection is one indicator of the quality of health services in the community, which also determines the image of health care institutions becauseit was a major cause of morbidityand death rate (mortality in hospital. Nursing care based on knowledge management is established from identification knowledge which is required, prevention performance of nosocomial infections post section caesarea. Nosocomial infections component consists of wound culture result. Method: This study was an observational study with a quasi experimental design. The population was all of nursing staff who working in obstetrics installation in hospitals A and B as much as 46 people. Sample was the total population. Data was collected through questionnaire, observation sheets and examination of the wound culture. Data was analyzed using t test B 1.274 dan p=0.028 Result: The result showed that 1 there was difference in knowledge management implementation before and after training; 2 there was difference in nurse’s performance in preventing nosocomial infection before and after training; 3 there is significant relationship between nurse’s performance in preventing nosocomial infection and infection incidence; 4 there is no significant difference of nursing care impementation on nosocomial incidence. Discussion: In conclusion, the development of nursing care based on knowledge management as a synthesis or induction of findings directed at 1 nurses’ knowledge does not affect the performance of the prevention of nosocomial infections; 2 knowledge management has a positive effect on the performance of the prevention of nosocomial infections; 3 implementation of infection prevention is integrated capabilities between knowledge, skills and attitudes of nurses in implementing performance in care. Keywords: model prevention, nosocomial infections, nursing care, knowledge management, sectio Caesarea

  9. Lack of innate interferon responses during SARS coronavirus infection in a vaccination and reinfection ferret model.

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    Mark J Cameron

    Full Text Available In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH(3-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.

  10. The role of immunity in the epidemiology of gonorrhoea, chlamydial infection and trichomoniasis: insights from a mathematical model.

    Science.gov (United States)

    Johnson, L F; Dorrington, R E; Bradshaw, D

    2011-12-01

    Most mathematical models of sexually transmitted infections (STIs) assume that infected individuals become susceptible to re-infection immediately after recovery. This paper assesses whether extending the standard model to allow for temporary immunity after recovery improves the correspondence between observed and modelled levels of STI prevalence in South Africa, for gonorrhoea, chlamydial infection and trichomoniasis. Five different models of immunity and symptom resolution were defined, and each model fitted to South African STI prevalence data. The models were compared in terms of Bayes factors, which show that in the case of gonorrhoea and chlamydial infection, models that allow for immunity provide a significantly better fit to STI prevalence data than models that do not allow for immunity. For all three STIs, estimates of the impact of changes in STI treatment and sexual behaviour are significantly lower in models that allow for immunity. Mathematical models that do not allow for immunity could therefore overestimate the effectiveness of STI interventions.

  11. A Multi-Compartment Hybrid Computational Model Predicts Key Roles for Dendritic Cells in Tuberculosis Infection

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    Simeone Marino

    2016-10-01

    Full Text Available Tuberculosis (TB is a world-wide health problem with approximately 2 billion people infected with Mycobacterium tuberculosis (Mtb, the causative bacterium of TB. The pathologic hallmark of Mtb infection in humans and Non-Human Primates (NHPs is the formation of spherical structures, primarily in lungs, called granulomas. Infection occurs after inhalation of bacteria into lungs, where resident antigen-presenting cells (APCs, take up bacteria and initiate the immune response to Mtb infection. APCs traffic from the site of infection (lung to lung-draining lymph nodes (LNs where they prime T cells to recognize Mtb. These T cells, circulating back through blood, migrate back to lungs to perform their immune effector functions. We have previously developed a hybrid agent-based model (ABM, labeled GranSim describing in silico immune cell, bacterial (Mtb and molecular behaviors during tuberculosis infection and recently linked that model to operate across three physiological compartments: lung (infection site where granulomas form, lung draining lymph node (LN, site of generation of adaptive immunity and blood (a measurable compartment. Granuloma formation and function is captured by a spatio-temporal model (i.e., ABM, while LN and blood compartments represent temporal dynamics of the whole body in response to infection and are captured with ordinary differential equations (ODEs. In order to have a more mechanistic representation of APC trafficking from the lung to the lymph node, and to better capture antigen presentation in a draining LN, this current study incorporates the role of dendritic cells (DCs in a computational fashion into GranSim. Results: The model was calibrated using experimental data from the lungs and blood of NHPs. The addition of DCs allowed us to investigate in greater detail mechanisms of recruitment, trafficking and antigen presentation and their role in tuberculosis infection. Conclusion: The main conclusion of this study is

  12. A Multi-Compartment Hybrid Computational Model Predicts Key Roles for Dendritic Cells in Tuberculosis Infection.

    Science.gov (United States)

    Marino, Simeone; Kirschner, Denise E

    2016-01-01

    Tuberculosis (TB) is a world-wide health problem with approximately 2 billion people infected with Mycobacterium tuberculosis (Mtb, the causative bacterium of TB). The pathologic hallmark of Mtb infection in humans and Non-Human Primates (NHPs) is the formation of spherical structures, primarily in lungs, called granulomas. Infection occurs after inhalation of bacteria into lungs, where resident antigen-presenting cells (APCs), take up bacteria and initiate the immune response to Mtb infection. APCs traffic from the site of infection (lung) to lung-draining lymph nodes (LNs) where they prime T cells to recognize Mtb . These T cells, circulating back through blood, migrate back to lungs to perform their immune effector functions. We have previously developed a hybrid agent-based model (ABM, labeled GranSim ) describing in silico immune cell, bacterial (Mtb) and molecular behaviors during tuberculosis infection and recently linked that model to operate across three physiological compartments: lung (infection site where granulomas form), lung draining lymph node (LN, site of generation of adaptive immunity) and blood (a measurable compartment). Granuloma formation and function is captured by a spatio-temporal model (i.e., ABM), while LN and blood compartments represent temporal dynamics of the whole body in response to infection and are captured with ordinary differential equations (ODEs). In order to have a more mechanistic representation of APC trafficking from the lung to the lymph node, and to better capture antigen presentation in a draining LN, this current study incorporates the role of dendritic cells (DCs) in a computational fashion into GranSim . The model was calibrated using experimental data from the lungs and blood of NHPs. The addition of DCs allowed us to investigate in greater detail mechanisms of recruitment, trafficking and antigen presentation and their role in tuberculosis infection. The main conclusion of this study is that early events after Mtb

  13. Estimating past hepatitis C infection risk from reported risk factor histories: implications for imputing age of infection and modeling fibrosis progression

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    Busch Michael P

    2007-12-01

    Full Text Available Abstract Background Chronic hepatitis C virus infection is prevalent and often causes hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver failure. Study of fibrosis progression often relies on imputing the time of infection, often as the reported age of first injection drug use. We sought to examine the accuracy of such imputation and implications for modeling factors that influence progression rates. Methods We analyzed cross-sectional data on hepatitis C antibody status and reported risk factor histories from two large studies, the Women's Interagency HIV Study and the Urban Health Study, using modern survival analysis methods for current status data to model past infection risk year by year. We compared fitted distributions of past infection risk to reported age of first injection drug use. Results Although injection drug use appeared to be a very strong risk factor, models for both studies showed that many subjects had considerable probability of having been infected substantially before or after their reported age of first injection drug use. Persons reporting younger age of first injection drug use were more likely to have been infected after, and persons reporting older age of first injection drug use were more likely to have been infected before. Conclusion In cross-sectional studies of fibrosis progression where date of HCV infection is estimated from risk factor histories, modern methods such as multiple imputation should be used to account for the substantial uncertainty about when infection occurred. The models presented here can provide the inputs needed by such methods. Using reported age of first injection drug use as the time of infection in studies of fibrosis progression is likely to produce a spuriously strong association of younger age of infection with slower rate of progression.

  14. Directed evolution and targeted mutagenesis to murinize listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model

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    Hill Colin

    2010-12-01

    Full Text Available Abstract Background Internalin A (InlA is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26, multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlAm*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlAm* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced

  15. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes Internalin A for enhanced infectivity in the murine oral infection model

    LENUS (Irish Health Repository)

    Monk, Ian R

    2010-12-13

    Abstract Background Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26), multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlA m*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlA m* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced entry into human

  16. Experimental tuberculosis in the Wistar rat: a model for protective immunity and control of infection.

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    Amit Singhal

    Full Text Available BACKGROUND: Despite the availability of many animal models for tuberculosis (TB research, there still exists a need for better understanding of the quiescent stage of disease observed in many humans. Here, we explored the use of the Wistar rat model for the study of protective immunity and control of Mycobacterium tuberculosis (Mtb infection. METHODOLOGY/PRINCIPAL FINDINGS: The kinetics of bacillary growth, evaluated by the colony stimulating assay (CFU and the extent of lung pathology in Mtb infected Wistar rats were dependent on the virulence of the strains and the size of the infecting inoculums. Bacillary growth control was associated with induction of T helper type 1 (Th1 activation, the magnitude of which was also Mtb strain and dose dependent. Histopathology analysis of the infected lungs demonstrated the formation of well organized granulomas comprising epithelioid cells, multinucleated giant cells and foamy macrophages surrounded by large numbers of lymphocytes. The late stage subclinical form of disease was reactivated by immunosuppression leading to increased lung CFU. CONCLUSION: The Wistar rat is a valuable model for better understanding host-pathogen interactions that result in control of Mtb infection and potentially establishment of latent TB. These properties together with the ease of manipulation, relatively low cost and well established use of rats in toxicology and pharmacokinetic analyses make the rat a good animal model for TB drug discovery.

  17. Discrete-time dynamic network model for the spread of susceptible-infective-recovered diseases

    Science.gov (United States)

    Chauhan, Sanjeev Kumar

    2017-07-01

    We propose a discrete-time dynamic network model describing the spread of susceptible-infective-recovered diseases in a population. We consider the case in which the nodes in the network change their links due to social mixing dynamics as well as in response to the disease. The model shows the behavior that, as we increase social mixing, disease spread is inhibited in certain cases, while in other cases it is enhanced. We also extend this dynamic network model to take into account the case of hidden infection. Here we find that, as expected, the disease spreads more readily if there is a time period after contracting the disease during which an individual is infective but is not known to have the disease.

  18. The effect of infected external computers on the spread of viruses: A compartment modeling study

    Science.gov (United States)

    Yang, Lu-Xing; Yang, Xiaofan

    2013-12-01

    Inevitably, there exist infected computers outside of the Internet. This paper aims to understand how infected external computers affect the spread of computer viruses. For that purpose, a new virus-antivirus spreading model, which takes into account the effect of infected/immune external computers, is established. A systematic study shows that, unlike most previous models, the proposed model admits no virus-free equilibrium and admits a globally asymptotically stable viral equilibrium. This result implies that it would be practically impossible to eradicate viruses on the Internet. As a result, inhibiting the virus prevalence to below an acceptable level would be the next best thing. A theoretical study reveals the effect of different parameters on the steady virus prevalence. On this basis, a number of suggestions are made so as to contain virus spreading.

  19. A rat model of picornavirus-induced airway infection and inflammation

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    Szakaly Renee J

    2009-08-01

    Full Text Available Abstract Background Infection of the lower airways by rhinovirus, a member of the picornavirus family, is an important cause of wheezing illnesses in infants, and plays an important role in the pathogenesis of rhinovirus-induced asthma exacerbations. Given the absence of natural rhinovirus infections in rodents, we investigated whether an attenuated form of mengovirus, a picornavirus whose wild-type form causes systemic rather than respiratory infections in its natural rodent hosts, could induce airway infections in rats with inflammatory responses similar to those in human rhinovirus infections. Results After inoculation with 107 plaque-forming units of attenuated mengovirus through an inhalation route, infectious mengovirus was consistently recovered on days 1 and 3 postinoculation from left lung homogenates (median Log10 plaque-forming units = 6.0 and 4.8, respectively and right lung bronchoalveolar lavage fluid (median Log10 plaque-forming units = 5.8 and 4.0, respectively. Insufflation of attenuated mengovirus, but not vehicle or UV-inactivated virus, into the lungs of BN rats caused significant increases (P P Conclusion Attenuated mengovirus caused a respiratory infection in rats with several days of viral shedding accompanied by a lower airway inflammatory response consisting of neutrophils and lymphocytes. These features suggest that mengovirus-induced airway infection in rodents could be a useful model to define mechanisms of rhinovirus-induced airway inflammation in humans.

  20. Neutropenia exacerbates infection by Acinetobacter baumannii clinical isolates in a murine wound model

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    Laryssa eGrguric-Smith

    2015-10-01

    Full Text Available The Gram negative coccobacillus Acinetobacter baumannii has become an increasingly prevalent cause of hospital-acquired infections in recent years. The majority of clinical A. baumannii isolates display high-level resistance to antimicrobials, which severely compromises our capacity to care for patients with A. baumannii disease. Neutrophils are of major importance in the host defense against microbial infections. However, the contribution of these cells of innate immunity in host resistance to cutaneous A. baumannii infection has not been directly investigated. Hence, we hypothesized that depletion of neutrophils increases severity of bacterial disease in an experimental A. baumannii murine wound model. In this study, the anti-Ly-6G monoclonal antibody (mAb, 1A8, was used to generate neutropenic mice and the pathogenesis of several A. baumannii clinical isolates on wounded cutaneous tissue was investigated. We demonstrated that neutrophil depletion enhances bacterial burden using colony forming unit determinations. Also, mAb 1A8 reduces global measurements of wound healing in A. baumannii-infected animals. Interestingly, histological analysis of cutaneous tissue excised from A. baumannii-infected animals treated with mAb 1A8 displays enhanced collagen deposition. Furthermore, neutropenia and A. baumannii infection alter pro-inflammatory cytokine release leading to severe microbial disease. Our findings provide a better understanding of the impact of these innate immune cells in controlling A. baumannii skin infections.

  1. Clinical and Pathologic Evaluation of Chronic Bartonella henselae or Bartonella clarridgeiae Infection in Cats

    OpenAIRE

    Kordick, Dorsey L.; Brown, Talmage T.; Shin, KwangOk; Breitschwerdt, Edward B.

    1999-01-01

    Human Bartonella infections result in diverse medical presentations, whereas many cats appear to tolerate chronic bacteremia without obvious clinical abnormalities. Eighteen specific-pathogen-free cats were inoculated with Bartonella henselae- and/or Bartonella clarridgeiae-infected cat blood and monitored for 454 days. Relapsing bacteremia did not correlate with changes in protein profiles or differences in antigenic protein recognition. Intradermal skin testing did not induce a delayed type...

  2. A probabilistic transmission and population dynamic model to assess tuberculosis infection risk.

    Science.gov (United States)

    Liao, Chung-Min; Cheng, Yi-Hsien; Lin, Yi-Jun; Hsieh, Nan-Hung; Huang, Tang-Luen; Chio, Chia-Pin; Chen, Szu-Chieh; Ling, Min-Pei

    2012-08-01

    The purpose of this study was to examine tuberculosis (TB) population dynamics and to assess potential infection risk in Taiwan. A well-established mathematical model of TB transmission built on previous models was adopted to study the potential impact of TB transmission. A probabilistic risk model was also developed to estimate site-specific risks of developing disease soon after recent primary infection, exogenous reinfection, or through endogenous reactivation (latently infected TB) among Taiwan regions. Here, we showed that the proportion of endogenous reactivation (53-67%) was larger than that of exogenous reinfection (32-47%). Our simulations showed that as epidemic reaches a steady state, age distribution of cases would finally shift toward older age groups dominated by latently infected TB cases as a result of endogenous reactivation. A comparison of age-weighted TB incidence data with our model simulation output with 95% credible intervals revealed that the predictions were in an apparent agreement with observed data. The median value of overall basic reproduction number (R₀) in eastern Taiwan ranged from 1.65 to 1.72, whereas northern Taiwan had the lowest R₀ estimate of 1.50. We found that total TB incidences in eastern Taiwan had 25-27% probabilities of total proportion of infected population exceeding 90%, whereas there were 36-66% probabilities having exceeded 20% of total proportion of infected population attributed to latently infected TB. We suggested that our Taiwan-based analysis can be extended to the context of developing countries, where TB remains a substantial cause of elderly morbidity and mortality. © 2012 Society for Risk Analysis.

  3. Aspergillus infection monitored by multimodal imaging in a rat model

    Czech Academy of Sciences Publication Activity Database

    Pluháček, Tomáš; Petrík, M.; Luptáková, Dominika; Benada, Oldřich; Palyzová, Andrea; Lemr, Karel; Havlíček, Vladimír

    2016-01-01

    Roč. 16, 11-12 (2016), s. 1785-1792 ISSN 1615-9853 R&D Projects: GA MŠk LO1509; GA ČR GAP206/12/1150 Institutional support: RVO:61388971 Keywords : Animal model * Aspergillosis * Biomedicine Subject RIV: CE - Biochemistry Impact factor: 4.041, year: 2016

  4. Dynamics of gastropod infection by first-stage larvae of protostrongylid nematodes--a model.

    Science.gov (United States)

    Rezác, P; Kindlmann, P; Dostálková, I; Holasová, E

    1993-12-01

    For the description of the dynamics of snail infection by the 1st-stage larvae of protostrongylid nematodes, Skorping (1988) used the miracidia-snail model (Anderson, 1978). Here it is shown that, in contrast to miracidia, in protostrongylids the instantaneous rate of infection, alpha, is strongly dependent on the experimental design (factors like host size and size of the experimental arena). With respect to this, Anderson's model is modified by incorporation of the experimental design. The parameter alpha in its new sense as the rate of penetration (probability that the infective larva will penetrate into the host during a time unit) is shown to remain dependent, although much less so, on the experimental design. Only the inclusion of the assumed effect of mucus, which decreases the rate of penetration, yields a parameter alpha 0 (the initial rate of penetration), which is completely independent of the design of the experiment, is species-specific, and also gives the best fit to the empirical data. As the above-mentioned factors can strongly influence the value of the instantaneous rate of infection in the laboratory experiments, alpha 0 is more suitable as a measure of either the larval infectivity for the snail or snail susceptibility to infection by the protostrongylid larvae.

  5. Biologically-directed modeling reflects cytolytic clearance of SIV-infected cells in vivo in macaques.

    Directory of Open Access Journals (Sweden)

    W David Wick

    Full Text Available The disappointing outcomes of cellular immune-based vaccines against HIV-1 despite strong evidence for the protective role of CD8⁺ T lymphocytes (CTLs has prompted revisiting the mechanisms of cellular immunity. Prior data from experiments examining the kinetics of Simian Immunodeficiency Virus (SIV clearance in infected macaques with or without in vivo CD8 depletion were interpreted as refuting the concept that CTLs suppress SIV/HIV by direct killing of infected cells. Here we briefly review the biological evidence for CTL cytolytic activity in viral infections, and utilize biologically-directed modeling to assess the possibility of a killing mechanism for the antiviral effect of CTLs, taking into account the generation, proliferation, and survival of activated CD4⁺ and CD8⁺ T lymphocytes, as well as the life cycle of the virus. Our analyses of the published macaque data using these models support a killing mechanism, when one considers T lymphocyte and HIV-1 lifecycles, and factors such as the eclipse period before release of virions by infected cells, an exponential pattern of virion production by infected cells, and a variable lifespan for acutely infected cells. We conclude that for SIV/HIV pathogenesis, CTLs deserve their reputation as being cytolytic.

  6. Marginal structural model to evaluate the association between cumulative osteoporosis medication and infection using claims data.

    Science.gov (United States)

    Xue, F; Goli, V; Petraro, P; McMullan, T; Sprafka, J M; Tchetgen Tchetgen, E J

    2017-10-01

    Due to the suboptimal persistence to osteoporosis (OP) treatment, factors triggering treatment discontinuation/switching may be causing time-varying confounding. BP treatment was associated with the risk of overall infection in opposite directions in the unweighted Cox model versus the weighted MSM. The discrepancy of effect estimates for overall infection in the MSM suggested there may be time-varying confounding. Due to the suboptimal persistence to osteoporosis (OP) treatment, factors triggering treatment discontinuation/switching may be affected by prior treatment and confound the subsequent treatment effect, causing time-varying confounding. In a US insurance database, the association between joint treatment of bisphosphonates (BP) and other OP medication and the incidence of infections among postmenopausal women was assessed using a marginal structural model (MSM). Stabilized weights were estimated by modeling treatment and censoring processes conditioning on past treatment, and baseline and time-varying covariates. BP treatment was associated with the risk of overall infection in opposite directions in the unweighted Cox model {incidence rate ratio [IRR] [95% confidence interval (CI)] = 1.15 [1.14-1.17]} versus the weighted MSM [IRR (95% CI) = 0.79 (0.77-0.81)], but was consistently associated with a lower risk of serious infection in both the unweighted Cox model [IRR (95% CI] = 0.79 (0.78-0.81)) and the weighted MSM [IRR (95% CI) = 0.71 (0.68-0.75)]. Similar results were found when current and past treatments were simultaneously assessed. The discrepancy of effect estimates for overall but not serious infection comparing unweighted models and MSM suggested analyses of composite outcomes with a wide range of disease severity may be more susceptible to time-varying confounding.

  7. Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection

    Science.gov (United States)

    Leber, Andrew; Viladomiu, Monica; Hontecillas, Raquel; Abedi, Vida; Philipson, Casandra; Hoops, Stefan; Howard, Brad; Bassaganya-Riera, Josep

    2015-01-01

    Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis and even death. To better understand the dynamics of mucosal immunity during C. difficile infection from initiation through expansion to resolution, we built a computational model of the mucosal immune response to the bacterium. The model was calibrated using data from a mouse model of C. difficile infection. The model demonstrates a crucial role of T helper 17 (Th17) effector responses in the colonic lamina propria and luminal commensal bacteria populations in the clearance of C. difficile and colonic pathology, whereas regulatory T (Treg) cells responses are associated with the recovery phase. In addition, the production of anti-microbial peptides by inflamed epithelial cells and activated neutrophils in response to C. difficile infection inhibit the re-growth of beneficial commensal bacterial species. Computational simulations suggest that the removal of neutrophil and epithelial cell derived anti-microbial inhibitions, separately and together, on commensal bacterial regrowth promote recovery and minimize colonic inflammatory pathology. Simulation results predict a decrease in colonic inflammatory markers, such as neutrophilic influx and Th17 cells in the colonic lamina propria, and length of infection with accelerated commensal bacteria re-growth through altered anti-microbial inhibition. Computational modeling provides novel insights on the therapeutic value of repopulating the colonic microbiome and inducing regulatory mucosal immune responses during C. difficile infection. Thus, modeling mucosal immunity-gut microbiota interactions has the potential to guide the development of targeted fecal transplantation therapies in the context of precision medicine interventions. PMID:26230099

  8. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model

    International Nuclear Information System (INIS)

    Perna, J.J.; Mannix, M.L.; Rooney, J.F.; Notkins, A.L.; Straus, S.E.

    1987-01-01

    Infection with herpes simplex virus often results in a latent infection of local sensory ganglia and a disease characterized by periodic viral reactivation and mucocutaneous lesions. The factors that trigger reactivation in humans are still poorly defined. In our study, five patients with documented histories of recurrent herpes simplex virus infection on the buttocks or sacrum were exposed to three times their minimal erythema dose of ultraviolet light. Site-specific cutaneous herpes simplex virus infection occurred at 4.4 +/- 0.4 days after exposure to ultraviolet light in 8 of 13 attempts at reactivation. We conclude that ultraviolet light can reactivate herpes simplex virus under experimentally defined conditions. This model in humans should prove useful in evaluating the pathophysiology and prevention of viral reactivation

  9. HIV-1-infected T-cells dynamics and prognosis: An evolutionary game model.

    Science.gov (United States)

    Khazaei, Bahareh; Sartakhti, Javad Salimi; Manshaei, Mohammad Hossein; Zhu, Quanyan; Sadeghi, Mehdi; Mousavi, Seyed Rasoul

    2017-12-01

    Understanding the dynamics of human immunodeficiency virus (HIV) is essential for depicting, developing, and investigating effective treatment strategies. HIV infects several types of immune cells, but its main target is to destroy helper T-cells. In the lymph nodes, the infected T-cells interact with each other and their environment to obtain more resources. According to infectivity and replicative capacity of T-cells in the HIV infection process, they can be divided into four phenotypes. Although genetic mutations in the reverse transcription that beget these phenotypes are random, the framework by which a phenotype become favored is affected by the environment and neighboring phenotypes. Moreover, the HIV disease has all components of an evolutionary process, including replication, mutation, and selection. We propose a novel structure-based game-theoretic model for the evolution of HIV-1-Infected CD4+T-cells and invasion of the immune system. We discuss the theoretical basis of the stable equilibrium states of the evolutionary dynamics of four T-cells types as well as its significant results to understand and control HIV infection. The results include the importance of genetic variations and the process of establishing evolutionary dynamics of the virus quasispecies. Our results show that there is a direct dependency between some parameters such as mutation rates and the stability of equilibrium states in the HIV infection. This is an interesting result because these parameters can be changed by some pharmacotherapies and alternative treatments. Our model indicates that in an appropriate treatment the relative frequency of the wild type of virus quasispecies can be decreased in the population. Consequently, this can cause delaying the emergence of the AIDS phase. To assess the model, we investigate two new treatments for HIV. The results show that our model can predict the treatment results. The paper shows that a structured-based evolutionary game theory can

  10. Pathogenic Events in a Nonhuman Primate Model of Oral Poliovirus Infection Leading to Paralytic Poliomyelitis.

    Science.gov (United States)

    Shen, Ling; Chen, Crystal Y; Huang, Dan; Wang, Richard; Zhang, Meihong; Qian, Lixia; Zhu, Yanfen; Zhang, Alvin Zhuoran; Yang, Enzhuo; Qaqish, Arwa; Chumakov, Konstantin; Kouiavskaia, Diana; Vignuzzi, Marco; Nathanson, Neal; Macadam, Andrew J; Andino, Raul; Kew, Olen; Xu, Junfa; Chen, Zheng W

    2017-07-15

    Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 10 7 to 10 9 50% tissue culture infective doses (TCID 50 ) consistently infected all the animals, and many monkeys receiving 10 8 or 10 9 TCID 50 developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines. IMPORTANCE Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed with

  11. High-throughput gene expression analysis in pigs as model for respiratory infections

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Brogaard, Louise; Schou, Kirstine Klitgaard

    for disease and inflammation. Pigs are fully susceptible to human influenza, and have been demonstrated to be involved in influenza evolution and ecology. Pigs share many similarities with humans regarding lung physiology and innate immune cell infiltration of the respiratory system and thus seem...... to be an obvious large animal model for respiratory infections. This study aimed at providing a better understanding of the involvement of circulating non-coding RNA and innate immune factors in porcine blood leukocytes during influenza virus infection. By employing the pig as a model we were able to perform...

  12. Citrobacter rodentium Infection Model for the Analysis of Bacterial Pathogenesis and Mucosal Immunology.

    Science.gov (United States)

    Kennedy, Catherine L; Hartland, Elizabeth L

    2018-01-01

    Citrobacter rodentium is a mouse restricted pathogen that was originally isolated from laboratory mouse colonies and causes transmissible colonic hyperplasia, characterized by thickening of the colon and inflammation. As a natural pathogen of mice, the infection model has proven critical to the development of our understanding of the pathogenesis of enteric disease and the mucosal immune response. In addition to this, some features of disease such as dysbiosis, inflammation, and wound healing replicate features of human inflammatory bowel diseases. As such, the C. rodentium infection model has become a key tool in investigations of many aspects of mucosal immunology.

  13. Drosophila melanogaster as an animal model for the study of Pseudomonas aeruginosa biofilm infections in vivo.

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    Heidi Mulcahy

    2011-10-01

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen capable of causing both acute and chronic infections in susceptible hosts. Chronic P. aeruginosa infections are thought to be caused by bacterial biofilms. Biofilms are highly structured, multicellular, microbial communities encased in an extracellular matrix that enable long-term survival in the host. The aim of this research was to develop an animal model that would allow an in vivo study of P. aeruginosa biofilm infections in a Drosophila melanogaster host. At 24 h post oral infection of Drosophila, P. aeruginosa biofilms localized to and were visualized in dissected Drosophila crops. These biofilms had a characteristic aggregate structure and an extracellular matrix composed of DNA and exopolysaccharide. P. aeruginosa cells recovered from in vivo grown biofilms had increased antibiotic resistance relative to planktonically grown cells. In vivo, biofilm formation was dependent on expression of the pel exopolysaccharide genes, as a pelB::lux mutant failed to form biofilms. The pelB::lux mutant was significantly more virulent than PAO1, while a hyperbiofilm strain (PAZHI3 demonstrated significantly less virulence than PAO1, as indicated by survival of infected flies at day 14 postinfection. Biofilm formation, by strains PAO1 and PAZHI3, in the crop was associated with induction of diptericin, cecropin A1 and drosomycin antimicrobial peptide gene expression 24 h postinfection. In contrast, infection with the non-biofilm forming strain pelB::lux resulted in decreased AMP gene expression in the fly. In summary, these results provide novel insights into host-pathogen interactions during P. aeruginosa oral infection of Drosophila and highlight the use of Drosophila as an infection model that permits the study of P. aeruginosa biofilms in vivo.

  14. Timing of progression from Chlamydia trachomatis infection to pelvic inflammatory disease: a mathematical modelling study

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    Herzog Sereina A

    2012-08-01

    Full Text Available Abstract Background Pelvic inflammatory disease (PID results from the ascending spread of microorganisms from the vagina and endocervix to the upper genital tract. PID can lead to infertility, ectopic pregnancy and chronic pelvic pain. The timing of development of PID after the sexually transmitted bacterial infection Chlamydia trachomatis (chlamydia might affect the impact of screening interventions, but is currently unknown. This study investigates three hypothetical processes for the timing of progression: at the start, at the end, or throughout the duration of chlamydia infection. Methods We develop a compartmental model that describes the trial structure of a published randomised controlled trial (RCT and allows each of the three processes to be examined using the same model structure. The RCT estimated the effect of a single chlamydia screening test on the cumulative incidence of PID up to one year later. The fraction of chlamydia infected women who progress to PID is obtained for each hypothetical process by the maximum likelihood method using the results of the RCT. Results The predicted cumulative incidence of PID cases from all causes after one year depends on the fraction of chlamydia infected women that progresses to PID and on the type of progression. Progression at a constant rate from a chlamydia infection to PID or at the end of the infection was compatible with the findings of the RCT. The corresponding estimated fraction of chlamydia infected women that develops PID is 10% (95% confidence interval 7-13% in both processes. Conclusions The findings of this study suggest that clinical PID can occur throughout the course of a chlamydia infection, which will leave a window of opportunity for screening to prevent PID.

  15. Caenorhabditis elegans: a simple nematode infection model for Penicillium marneffei.

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    Xiaowen Huang

    Full Text Available Penicillium marneffei, one of the most important thermal dimorphic fungi, is a severe threat to the life of immunocompromised patients. However, the pathogenic mechanisms of P. marneffei remain largely unknown. In this work, we developed a model host by using nematode Caenorhabditis elegans to investigate the virulence of P. marneffei. Using two P. marneffei clinical isolate strains 570 and 486, we revealed that in both liquid and solid media, the ingestion of live P. marneffei was lethal to C. elegans (P<0.001. Meanwhile, our results showed that the strain 570, which can produce red pigment, had stronger pathogenicity in C. elegans than the strain 486, which can't produce red pigment (P<0.001. Microscopy showed the formation of red pigment and hyphae within C. elegans after incubation with P. marneffei for 4 h, which are supposed to be two contributors in nematodes killing. In addition, we used C. elegans as an in vivo model to evaluate different antifungal agents against P. marneffei, and found that antifungal agents including amphotericin B, terbinafine, fluconazole, itraconazole and voriconazole successfully prolonged the survival of nematodesinfected by P. marneffei. Overall, this alternative model host can provide us an easy tool to study the virulence of P. marneffei and screen antifungal agents.

  16. Spread of Ebola disease with susceptible exposed infected isolated recovered (SEIIhR) model

    Science.gov (United States)

    Azizah, Afina; Widyaningsih, Purnami; Retno Sari Saputro, Dewi

    2017-06-01

    Ebola is a deadly infectious disease and has caused an epidemic on several countries in West Africa. Mathematical modeling to study the spread of Ebola disease has been developed, including through models susceptible infected removed (SIR) and susceptible exposed infected removed (SEIR). Furthermore, susceptible exposed infected isolated recovered (SEIIhR) model has been derived. The aims of this research are to derive SEIIhR model for Ebola disease, to determine the patterns of its spread, to determine the equilibrium point and stability of the equilibrium point using phase plane analysis, and also to apply the SEIIhR model on Ebola epidemic in Sierra Leone in 2014. The SEIIhR model is a differential equation system. Pattern of ebola disease spread with SEIIhR model is solution of the differential equation system. The equilibrium point of SEIIhR model is unique and it is a disease-free equilibrium point that stable. Application of the model is based on the data Ebola epidemic in Sierra Leone. The free-disease equilibrium point (Se; Ee; Ie; Ihe; Re )=(5743865, 0, 0, 0, 0) is stable.

  17. Spread of Ebola disease with susceptible exposed infected isolated recovered (SEIIhR) model

    International Nuclear Information System (INIS)

    Azizah, Afina; Widyaningsih, Purnami; Saputro, Dewi Retno Sari

    2017-01-01

    Ebola is a deadly infectious disease and has caused an epidemic on several countries in West Africa. Mathematical modeling to study the spread of Ebola disease has been developed, including through models susceptible infected removed (SIR) and susceptible exposed infected removed (SEIR). Furthermore, susceptible exposed infected isolated recovered (SEII h R) model has been derived. The aims of this research are to derive SEII h R model for Ebola disease, to determine the patterns of its spread, to determine the equilibrium point and stability of the equilibrium point using phase plane analysis, and also to apply the SEII h R model on Ebola epidemic in Sierra Leone in 2014. The SEII h R model is a differential equation system. Pattern of ebola disease spread with SEII h R model is solution of the differential equation system. The equilibrium point of SEII h R model is unique and it is a disease-free equilibrium point that stable. Application of the model is based on the data Ebola epidemic in Sierra Leone. The free-disease equilibrium point ( S e ; E e ; I e ; I he ; R e )=(5743865, 0, 0, 0, 0) is stable. (paper)

  18. Coupling of Petri Net Models of the Mycobacterial Infection Process and Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Rafael V. Carvalho

    2015-04-01

    Full Text Available Computational and mathematical modeling is important in support of a better understanding of complex behavior in biology. For the investigation of biological systems, researchers have used computers to construct, verify, and validate models that describe the mechanisms behind biological processes in multi-scale representations. In this paper we combine Petri net models that represent the mycobacterial infection process and innate immune response at various levels of organization, from molecular interaction to granuloma dissemination. In addition to the conventional graphical representation of the Petri net, the outcome of the model is projected onto a 3D model representing the zebrafish embryo. In this manner we provide a visualization of the process in a simulation framework that portrays the infection in the living system.

  19. Topical application of zinc oxide nanoparticles reduces bacterial skin infection in mice and exhibits antibacterial activity by inducing oxidative stress response and cell membrane disintegration in macrophages.

    Science.gov (United States)

    Pati, Rashmirekha; Mehta, Ranjit Kumar; Mohanty, Soumitra; Padhi, Avinash; Sengupta, Mitali; Vaseeharan, Baskarlingam; Goswami, Chandan; Sonawane, Avinash

    2014-08-01

    Here we studied immunological and antibacterial mechanisms of zinc oxide nanoparticles (ZnO-NPs) against human pathogens. ZnO-NPs showed more activity against Staphylococcus aureus and least against Mycobacterium bovis-BCG. However, BCG killing was significantly increased in synergy with antituberculous-drug rifampicin. Antibacterial mechanistic studies showed that ZnO-NPs disrupt bacterial cell membrane integrity, reduce cell surface hydrophobicity and down-regulate the transcription of oxidative stress-resistance genes in bacteria. ZnO-NP treatment also augmented the intracellular bacterial killing by inducing reactive oxygen species production and co-localization with Mycobacterium smegmatis-GFP in macrophages. Moreover, ZnO-NPs disrupted biofilm formation and inhibited hemolysis by hemolysin toxin producing S. aureus. Intradermal administration of ZnO-NPs significantly reduced the skin infection, bacterial load and inflammation in mice, and also improved infected skin architecture. We envision that this study offers novel insights into antimicrobial actions of ZnO-NPs and also demonstrates ZnO-NPs as a novel class of topical anti-infective agent for the treatment of skin infections. This in-depth study demonstrates properties of ZnO nanoparticles in infection prevention and treatment in several skin infection models, dissecting the potential mechanisms of action of these nanoparticles and paving the way to human applications. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Impulsive vaccination and dispersal on dynamics of an SIR epidemic model with restricting infected individuals boarding transports

    Science.gov (United States)

    Jiao, Jianjun; Cai, Shaohong; Li, Limei

    2016-05-01

    To understand the effect of impulsive vaccination and restricting infected individuals boarding transports on disease spread, we establish an SIR model with impulsive vaccination, impulsive dispersal and restricting infected individuals boarding transports. This SIR epidemic model for two regions, which are connected by transportation of non-infected individuals, portrays the evolvement of diseases. We prove that all solutions of the investigated system are uniformly ultimately bounded. We also prove that there exists globally asymptotically stable infection-free boundary periodic solution. The condition for permanence is discussed. It is concluded that the approach of impulsive vaccination and restricting infected individuals boarding transports provides reliable tactic basis for preventing disease spread.

  1. Acanthamoeba and Dictyostelium as Cellular Models for Legionella Infection

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    A. Leoni Swart

    2018-03-01

    Full Text Available Environmental bacteria of the genus Legionella naturally parasitize free-living amoebae. Upon inhalation of bacteria-laden aerosols, the opportunistic pathogens grow intracellularly in alveolar macrophages and can cause a life-threatening pneumonia termed Legionnaires' disease. Intracellular replication in amoebae and macrophages takes place in a unique membrane-bound compartment, the Legionella-containing vacuole (LCV. LCV formation requires the bacterial Icm/Dot type IV secretion system, which translocates literally hundreds of “effector” proteins into host cells, where they modulate crucial cellular processes for the pathogen's benefit. The mechanism of LCV formation appears to be evolutionarily conserved, and therefore, amoebae are not only ecologically significant niches for Legionella spp., but also useful cellular models for eukaryotic phagocytes. In particular, Acanthamoeba castellanii and Dictyostelium discoideum emerged over the last years as versatile and powerful models. Using genetic, biochemical and cell biological approaches, molecular interactions between amoebae and Legionella pneumophila have recently been investigated in detail with a focus on the role of phosphoinositide lipids, small and large GTPases, autophagy components and the retromer complex, as well as on bacterial effectors targeting these host factors.

  2. Modeling of HIV-1 infection: insights to the role of monocytes/macrophages, latently infected T4 cells, and HAART regimes.

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    Qiang Li

    Full Text Available A novel dynamic model covering five types of cells and three connected compartments, peripheral blood (PB, lymph nodes (LNs, and the central nervous system (CNS, is here proposed. It is based on assessment of the biological principles underlying the interactions between the human immunodeficiency virus type I (HIV-1 and the human immune system. The simulated results of this model matched the three well-documented phases of HIV-1 infection very closely and successfully described the three stages of LN destruction that occur during HIV-1 infection. The model also showed that LNs are the major location of viral replication, creating a pool of latently infected T4 cells during the latency period. A detailed discussion of the role of monocytes/macrophages is made, and the results indicated that infected monocytes/macrophages could determine the progression of HIV-1 infection. The effects of typical highly active antiretroviral therapy (HAART drugs on HIV-1 infection were analyzed and the results showed that efficiency of each drug but not the time of the treatment start contributed to the change of the turnover of the disease greatly. An incremental count of latently infected T4 cells was made under therapeutic simulation, and patients were found to fail to respond to HAART therapy in the presence of certain stimuli, such as opportunistic infections. In general, the dynamics of the model qualitatively matched clinical observations very closely, indicating that the model may have benefits in evaluating the efficacy of different drug therapy regimens and in the discovery of new monitoring markers and therapeutic schemes for the treatment of HIV-1 infection.

  3. A multiscale model on hospital infections coupling macro and micro dynamics

    Science.gov (United States)

    Wang, Xia; Tang, Sanyi

    2017-09-01

    A multiscale model of hospital infections coupling the micro model of the growth of bacteria and the macro model describing the transmission of the bacteria among patients and health care workers (HCWs) was established to investigate the effects of antibiotic treatment on the transmission of the bacteria among patients and HCWs. The model was formulated by viewing the transmission rate from infected patients to HCWs and the shedding rate of bacteria from infected patients to the environment as saturated functions of the within-host bacterial load. The equilibria and the basic reproduction number of the coupled system were studied, and the global dynamics of the disease free equilibrium and the endemic equilibrium were analyzed in detail by constructing two Lyapunov functions. Furthermore, effects of drug treatment in the within-host model on the basic reproduction number and the dynamics of the coupled model were studied by coupling a pharmacokinetics model with the within-host model. Sensitive analysis indicated that the growth rate of the bacteria, the maximum drug effect and the dosing interval are the three most sensitive parameters contributing to the basic reproduction number. Thus, adopting ;wonder; drugs to decrease the growth rate of the bacteria or to increase the drug's effect is the most effective measure but changing the dosage regime is also effective. A quantitative criterion of how to choose the best dosage regimen can also be obtained from numerical results.

  4. A Simplified 4-Site Economical Intradermal Post-Exposure Rabies Vaccine Regimen: A Randomised Controlled Comparison with Standard Methods

    Science.gov (United States)

    Warrell, Mary J.; Riddell, Anna; Yu, Ly-Mee; Phipps, Judith; Diggle, Linda; Bourhy, Hervé; Deeks, Jonathan J.; Fooks, Anthony R.; Audry, Laurent; Brookes, Sharon M.; Meslin, François-Xavier; Moxon, Richard; Pollard, Andrew J.; Warrell, David A.

    2008-01-01

    Background The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods. Methods Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available. Findings All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method. Conclusions This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be

  5. A simplified 4-site economical intradermal post-exposure rabies vaccine regimen: a randomised controlled comparison with standard methods.

    Directory of Open Access Journals (Sweden)

    Mary J Warrell

    2008-04-01

    Full Text Available The need for economical rabies post-exposure prophylaxis (PEP is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods.Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90; or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available.All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method.This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be introduced without further

  6. Parasite Burden in Hamsters Infected with Two Different Strains of Leishmania (Leishmania) infantum: “Leishman Donovan Units” versus Real-Time PCR

    Science.gov (United States)

    Moreira, Nádia das Dores; Vitoriano-Souza, Juliana; Roatt, Bruno Mendes; Vieira, Paula Melo de Abreu; Ker, Henrique Gama; de Oliveira Cardoso, Jamille Mirelle; Giunchetti, Rodolfo Cordeiro; Carneiro, Cláudia Martins; de Lana, Marta; Reis, Alexandre Barbosa

    2012-01-01

    To develop and test new therapeutics and immune prophylaxis strategies for visceral leishmaniasis (VL), understanding tissue parasitism evolution after experimental infection with Leishmania infantum is important. Experimental infection in a hamster model (Mesocricetus auratus) reproduces several typical aspects of canine and human VL that are closely related to the inoculum’s route. We quantified the parasitism in the liver and spleen of hamsters experimentally infected by various routes (intradermal, intraperitoneal, and intracardiac [IC]) and different strains of L. infantum (MHOM/BR/74/PP75 and Wild) and compared two different methodologies to evaluate tissue parasitism (Leishman Donovan units [LDU] and real-time qPCR). In addition, the quantification of specific total-IgG in the serum of uninfected and infected hamsters was determined by ELISA. The animals were followed for 1, 3, 6 and 9 months post-infection for survival analysis. We found that infection with the Wild strain by the IC route resulted in higher mortality. Positive antibody (IgG) responses were detected with higher peaks at 6 and 9 months in the IC group inoculated with PP75 strain. However, in animals infected with the Wild strain the IgG levels were elevated in all infected groups during all the time evaluated. We also observed by LDU analysis that the IC route lead to higher parasitism in the liver and spleen with both strains. Furthermore, qPCR showed higher sensitivity for identifying animals with low parasitic burden. In conclusion, qPCR can be useful for assessing parasitism in the spleen and liver of a hamster model infected with L. infantum independent of the route of infection, and this technique may become an essential tool for assessing parasite density in the hamster model after experimental treatment or immunization with potential vaccine candidates. PMID:23112869

  7. Discrete Dynamical Modeling of Influenza Virus Infection Suggests Age-Dependent Differences in Immunity.

    Science.gov (United States)

    Keef, Ericka; Zhang, Li Ang; Swigon, David; Urbano, Alisa; Ermentrout, G Bard; Matuszewski, Michael; Toapanta, Franklin R; Ross, Ted M; Parker, Robert S; Clermont, Gilles

    2017-12-01

    Immunosenescence, an age-related decline in immune function, is a major contributor to morbidity and mortality in the elderly. Older hosts exhibit a delayed onset of immunity and prolonged inflammation after an infection, leading to excess damage and a greater likelihood of death. Our study applies a rule-based model to infer which components of the immune response are most changed in an aged host. Two groups of BALB/c mice (aged 12 to 16 weeks and 72 to 76 weeks) were infected with 2 inocula: a survivable dose of 50 PFU and a lethal dose of 500 PFU. Data were measured at 10 points over 19 days in the sublethal case and at 6 points over 7 days in the lethal case, after which all mice had died. Data varied primarily in the onset of immunity, particularly the inflammatory response, which led to a 2-day delay in the clearance of the virus from older hosts in the sublethal cohort. We developed a Boolean model to describe the interactions between the virus and 21 immune components, including cells, chemokines, and cytokines, of innate and adaptive immunity. The model identifies distinct sets of rules for each age group by using Boolean operators to describe the complex series of interactions that activate and deactivate immune components. Our model accurately simulates the immune responses of mice of both ages and with both inocula included in the data (95% accurate for younger mice and 94% accurate for older mice) and shows distinct rule choices for the innate immunity arm of the model between younger and aging mice in response to influenza A virus infection. IMPORTANCE Influenza virus infection causes high morbidity and mortality rates every year, especially in the elderly. The elderly tend to have a delayed onset of many immune responses as well as prolonged inflammatory responses, leading to an overall weakened response to infection. Many of the details of immune mechanisms that change with age are currently not well understood. We present a rule-based model of the

  8. Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model.

    Science.gov (United States)

    Trigo, Gabriela; Martins, Teresa G; Fraga, Alexandra G; Longatto-Filho, Adhemar; Castro, António G; Azeredo, Joana; Pedrosa, Jorge

    2013-01-01

    Buruli Ulcer (BU) is a neglected, necrotizing skin disease caused by Mycobacterium ulcerans. Currently, there is no vaccine against M. ulcerans infection. Although the World Health Organization recommends a combination of rifampicin and streptomycin for the treatment of BU, clinical management of advanced stages is still based on the surgical resection of infected skin. The use of bacteriophages for the control of bacterial infections has been considered as an alternative or to be used in association with antibiotherapy. Additionally, the mycobacteriophage D29 has previously been shown to display lytic activity against M. ulcerans isolates. We used the mouse footpad model of M. ulcerans infection to evaluate the therapeutic efficacy of treatment with mycobacteriophage D29. Analyses of macroscopic lesions, bacterial burdens, histology and cytokine production were performed in both M. ulcerans-infected footpads and draining lymph nodes (DLN). We have demonstrated that a single subcutaneous injection of the mycobacteriophage D29, administered 33 days after bacterial challenge, was sufficient to decrease pathology and to prevent ulceration. This protection resulted in a significant reduction of M. ulcerans numbers accompanied by an increase of cytokine levels (including IFN-γ), both in footpads and DLN. Additionally, mycobacteriophage D29 treatment induced a cellular infiltrate of a lymphocytic/macrophagic profile. Our observations demonstrate the potential of phage therapy against M. ulcerans infection, paving the way for future studies aiming at the development of novel phage-related therapeutic approaches against BU.

  9. Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model.

    Directory of Open Access Journals (Sweden)

    Gabriela Trigo

    Full Text Available BACKGROUND: Buruli Ulcer (BU is a neglected, necrotizing skin disease caused by Mycobacterium ulcerans. Currently, there is no vaccine against M. ulcerans infection. Although the World Health Organization recommends a combination of rifampicin and streptomycin for the treatment of BU, clinical management of advanced stages is still based on the surgical resection of infected skin. The use of bacteriophages for the control of bacterial infections has been considered as an alternative or to be used in association with antibiotherapy. Additionally, the mycobacteriophage D29 has previously been shown to display lytic activity against M. ulcerans isolates. METHODOLOGY/PRINCIPAL FINDINGS: We used the mouse footpad model of M. ulcerans infection to evaluate the therapeutic efficacy of treatment with mycobacteriophage D29. Analyses of macroscopic lesions, bacterial burdens, histology and cytokine production were performed in both M. ulcerans-infected footpads and draining lymph nodes (DLN. We have demonstrated that a single subcutaneous injection of the mycobacteriophage D29, administered 33 days after bacterial challenge, was sufficient to decrease pathology and to prevent ulceration. This protection resulted in a significant reduction of M. ulcerans numbers accompanied by an increase of cytokine levels (including IFN-γ, both in footpads and DLN. Additionally, mycobacteriophage D29 treatment induced a cellular infiltrate of a lymphocytic/macrophagic profile. CONCLUSIONS/SIGNIFICANCE: Our observations demonstrate the potential of phage therapy against M. ulcerans infection, paving the way for future studies aiming at the development of novel phage-related therapeutic approaches against BU.

  10. Intradermal injections of a hair growth factor formulation for enhancement of human hair regrowth - safety and efficacy evaluation in a first-in-man pilot clinical study.

    Science.gov (United States)

    Kapoor, Rinky; Shome, Debraj

    2018-02-26

    Research has shown the efficacy of hair growth factors in hair regrowth. We describe the intradermal injections of a recombinant, bioengineered hair formulation, containing growth factors, into the scalp skin, for enhancement of hair regrowth and evaluate its efficacy. The objective of this study was to assess the efficacy and safety of the hair growth factor formulation in reducing hair loss and enhancing hair growth. This was an open-label, prospective, single-arm interventional pilot study in which 1000 patients were given intradermal injections of a hair formulation into the scalp skin. The formulation contains vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor, keratinocyte growth factor, thymosin β4, and copper tripeptide-1 suspended in a sterile injectable vehicle. Intradermal injections of this hair formulation were injected into the scalp once every 3 weeks for a total of eight such sessions. Hair pull test was performed before every session. Videomicroscopic and global images were taken at baseline, fourth session, eighth session, and 2 months after the completion of the eight sessions. Relevant safety assessments through physical examination, questionnaires, and appropriate laboratory examination were conducted throughout the study. Significant reduction in hair fall was seen in 83% of the patients on hair pull test. Videomicroscopic image evaluation showed that most patients had a decrease in the number of vellus hairs, increase in number of terminal hairs, and increase in shaft diameter. Seventy-five percent of the patients believed that the hair injections were aiding the treatment of their hair loss, and it was also beneficial in post-hair transplant patients. At 1 year, a statistically significant increase in total hair count (P = 0.002) continued to be seen. Treatment was well tolerated. Intradermal injections of this hair formulation may be a promising option for treating male as well as female

  11. Antibody titers in animal bite victims after post exposure vaccination with intradermally administered purified vero cell rabies vaccine using modified thai red cross regimen

    International Nuclear Information System (INIS)

    Hafeez, S.; Tahir, Z.

    2014-01-01

    To determine the seroconversion following rabies vaccination by intradermal route in cases of animal bite attending Anti rabies center, Lahore for post exposure prophylaxis. Study Design: Cross sectional descriptive study. Place and Duration: Antirabies center, Birdwood road Lahore, Microbiology laboratory, office of Bacteriologist, Government of Punjab, Lahore. Patients and Methods: Victims of all ages and both sexes having exposure with suspected rabid animal within 24 - 72 hours were included, fulfilling inclusion and exclusion criteria, over 3 months period from February to April 20. Patients of Category II and III wounds were included. Purified vero cell vaccine (PVR V) with antigenic content> 2.5 ml was used for intradermal vaccination according to modified Thai Red Cross regimen (2-2-2-0-2). Each victim received 0.1 ml intradermal dose on each deltoid on day 0, 3, 7 and 28th day of bite. Blood samples from victims were taken on day 0, 14 and 35. Antibody titers were estimated by ELISA kit. Results: Fifty cases were studied including 20 children. Male female ratio was 4:1. Optimum serocon version (> 0.5 IU/ml) was achieved in all cases by day 14. Antibody levels increased further (> 4 IV/ml) in 92% cases on day 35. Geometric mean titers were 3.2 IU/ml and 6.2 IU/ml on day 14 and 35 respectively. Conclusion: Intradermal route for cell culture rabies vaccine for postexposure prophylaxis in animal bite victims was efficacious and safe. The smaller dosage of vaccine was economically affordable by patients in referral centers. (author)

  12. A Neonatal Murine Model of Coxsackievirus A6 Infection for Evaluation of Antiviral and Vaccine Efficacy.

    Science.gov (United States)

    Zhang, Zhenjie; Dong, Zhaopeng; Wei, Qingjuan; Carr, Michael J; Li, Juan; Ding, Shujun; Tong, Yigang; Li, Dong; Shi, Weifeng

    2017-05-01

    Hand, foot, and mouth disease (HFMD) is a global health concern. Family Picornaviridae members, particularly enterovirus A71 (EVA71) and coxsackievirus A16 (CVA16), are the primary etiological agents of HFMD; however, a third enterovirus A species, CVA6, has been recently associated with epidemic outbreaks. Study of the pathogenesis of CVA6 infection and development of antivirals and vaccines are hindered by a lack of appropriate animal models. We have developed and characterized a murine model of CVA6 infection that was employed to evaluate the antiviral activities of different drugs and the protective efficacies of CVA6-inactivated vaccines. Neonatal mice were susceptible to CVA6 infection via intramuscular inoculation, and the susceptibility of mice to CVA6 infection was age and dose dependent. Five-day-old mice infected with 10 5.5 50% tissue culture infective doses of the CVA6 WF057R strain consistently exhibited clinical signs, including reduced mobility, lower weight gain, and quadriplegia with significant pathology in the brain, hind limb skeletal muscles, and lungs of the infected mice in the moribund state. Immunohistochemical analysis and quantitative reverse transcription-PCR (qRT-PCR) analyses showed high viral loads (11 log 10 /mg) in skeletal muscle, and elevated levels of interleukin-6 (IL-6; >2,000 pg/ml) were associated with severe viral pneumonia and encephalitis. Ribavirin and gamma interferon administered prophylactically diminished CVA6-associated pathology in vivo , and treatment with IL-6 accelerated the death of neonatal mice. Both specific anti-CVA6 serum and maternal antibody play important roles in controlling CVA6 infection and viral replication. Collectively, these findings indicate that this neonatal murine model will be invaluable in future studies to develop CVA6-specific antivirals and vaccines. IMPORTANCE Although coxsackievirus A6 (CVA6) infections are commonly mild and self-limiting, a small proportion of children may have

  13. Local Stability Analysis of an Infection-Age Mathematical Model for ...

    African Journals Online (AJOL)

    Timothy

    www.bioline.org.br/ja. Local Stability Analysis of an Infection-Age Mathematical Model for Tuberculosis. Disease Dynamics. 1. ASHEZUA, TT;. 2. AKINWANDE, NI;. 3. ABDULRAHMAN, S;. 4. OLAYIWOLA, RO;. 5. KUTA, FA. 1Department of Mathematics/Statistics/Computer Science, Federal University of Agriculture, Makurdi, ...

  14. Future challenges for clinical care of an ageing population infected with HIV: a modelling study

    NARCIS (Netherlands)

    Smit, Mikaela; Brinkman, Kees; Geerlings, Suzanne; Smit, Colette; Thyagarajan, Kalyani; Sighem, Ard van; de Wolf, Frank; Hallett, Timothy B.

    2015-01-01

    The population infected with HIV is getting older and these people will increasingly develop age-related non-communicable diseases (NCDs). We aimed to quantify the scale of the change and the implications for HIV care in the Netherlands in the future. We constructed an individual-based model of the

  15. Modeling HCV Disease in Animals: Virology, Immunology and Pathogenesis of HCV and GBV-B Infections

    Directory of Open Access Journals (Sweden)

    Cordelia eManickam

    2014-12-01

    Full Text Available Hepatitis C virus (HCV infection has become a global public health burden costing billions of dollars in health care annually. Even with rapidly advancing scientific technologies, this disease still looms large due to a lack of vaccines and affordable treatment options. The immune correlates of protection and predisposing factors towards chronicity remain major obstacles to development of HCV vaccines and immunotherapeutics due, at least in part, to lack of a tangible infection animal model. This review discusses the currently available animal models for HCV disease, with a primary focus on GB virus B (GBV-B infection of New World primates that recapitulates the dual hepacivirus phenotypes of acute viral clearance and chronic pathologic disease. HCV and GBV-B are also closely phylogenetically related, and advances in characterization of the immune systems of New World primates have already led to the use of this model for drug testing and vaccine trials. Herein, we discuss the benefits and caveats of the GBV-B infection model and discuss potential avenues for future development of novel vaccines and immunotherapies.

  16. In vivo efficacy of humanized ceftaroline fosamil-avibactam exposures in a polymicrobial infection model.

    Science.gov (United States)

    Bhalodi, Amira A; Crandon, Jared L; Williams, Gregory; Nicolau, David P

    2013-11-01

    Although Gram-positive cocci are the most common pathogens in diabetic foot infections, these infections often are polymicrobial. The objective of this study was to assess the efficacy of a simulated human dose of 600 mg ceftaroline fosamil-600 mg avibactam every 8 h as a 1-h infusion in a polymicrobial in vivo murine model. Seven isolates were used (3 methicillin-resistant Staphylococcus aureus [MRSA] isolates, 1 methicillin-susceptible S. aureus [MSSA] isolate, 1 Escherichia coli isolate, 1 Enterobacter cloacae isolate, and 1 Bacteroides fragilis isolate) in various combinations in an immunocompromised polymicrobial tissue infection to assess the efficacy of the simulated regimen. Each infection was comprised of at least one S. aureus isolate with a MIC of 0.25 to 1 μg/ml and one Enterobacteriaceae isolate with a MIC of 1 or 4 μg/ml. Eight of 16 infections also included B. fragilis, with a MIC of 0.5 μg/ml, as a third organism. Efficacy was evaluated after 24 h as the change in log10 CFU from the level of 0-h controls. Efficacy was seen against all isolate combinations, with at least a 1-log kill against Enterobacteriaceae and a minimum of a 2-log kill against S. aureus and B. fragilis isolates. These bacterial reductions correlate with free drug concentration above the MIC (fT>MIC) produced by the humanized regimen of 100, 86, and 56% at MICs of 1, 2, and 4 μg/ml, respectively. The humanized regimen of 600 mg ceftaroline fosamil-600 mg avibactam every 8 h as a 1-h infusion showed predictable efficacy against all infections tested in this model. These data support further clinical investigation of ceftaroline fosamil-avibactam for the treatment of polymicrobial tissue infections.

  17. Porphyromonas gingivalis and Treponema denticola Mixed Microbial Infection in a Rat Model of Periodontal Disease

    Directory of Open Access Journals (Sweden)

    Raj K. Verma

    2010-01-01

    Full Text Available Porphyromonas gingivalis and Treponema denticola are periodontal pathogens that express virulence factors associated with the pathogenesis of periodontitis. In this paper we tested the hypothesis that P. gingivalis and T. denticola are synergistic in terms of virulence; using a model of mixed microbial infection in rats. Groups of rats were orally infected with either P. gingivalis or T. denticola or mixed microbial infections for 7 and 12 weeks. P. gingivalis genomic DNA was detected more frequently by PCR than T. denticola. Both bacteria induced significantly high IgG, IgG2b, IgG1, IgG2a antibody levels indicating a stimulation of Th1 and Th2 immune response. Radiographic and morphometric measurements demonstrated that rats infected with the mixed infection exhibited significantly more alveolar bone loss than shaminfected control rats. Histology revealed apical migration of junctional epithelium, rete ridge elongation, and crestal alveolar bone resorption; resembling periodontal disease lesion. These results showed that P. gingivalis and T. denticola exhibit no synergistic virulence in a rat model of periodontal disease.

  18. Pathogenetic elements of hepatitis E and animal models of HEV infection.

    Science.gov (United States)

    Krawczynski, Krzysztof; Meng, Xiang-Jin; Rybczynska, Jolanta

    2011-10-01

    The pathogenesis of HEV infection responsible for liver pathology and clinical disease is not well understood. The main target for the virus is the hepatocyte, where it replicates and is released to bile and gastrointestinal tract. Viremia is regularly seen during the virus replication. The exact mechanism of hepatocytic death is uncertain. In experimentally infected non-human primates, the peak of liver lesions, measured by alanine aminotransferase activity elevation, is concordant with the virus disappearance from stool at the time of dynamic humoral immune response; the role of cellular immunity has not been researched adequately, especially HEV-specific immune response in the liver. Non-human primates (chimpanzees, rhesus and cynomolgus macaques) are most widely used animal models for the study of HEV infection, its pathogenesis and vaccine trials. Several other animal models including pigs, rabbits and chickens have recently been established for the study of various aspects of HEV infection. Infectivity studies in susceptible primates were of significance in molecular studies of the virus itself. Preclinical vaccine trials with the use of various recombinant HEV capsid proteins and viral DNA established basic platform for formulation of HEV vaccine applied in HEV-endemic regions (China, Nepal). Copyright © 2011. Published by Elsevier B.V.

  19. Morphological studies in a model for dengue-2 virus infection in mice

    Directory of Open Access Journals (Sweden)

    Ortrud Monika Barth

    2006-12-01

    Full Text Available One of the main difficulties in studying dengue virus infection in humans and in developing a vaccine is the absence of a suitable animal model which develops the full spectrum of dengue fever, dengue haemorrhagic fever, and dengue shock syndrome. It is our proposal to present morphological aspects of an animal model which shows many similarities with the dengue infection in humans. BALB/c mice were intraperitoneally infected with non-neuroadapted dengue virus serotype 2 (DENV-2. Histopathological and morphometrical analyses of liver tissue revealed focal alterations along the infection, reaching wide-ranging portal and centrolobular veins congestion and sinusoidal cell death. Additional ultrastructural observations demonstrated multifocal endothelial injury, platelet recruitment, and alterated hepatocytes. Dengue virus antigen was detected in hepatocytes and in the capillar endothelium of the central lobular vein area. Liver function tests showed high levels of aspartate transaminase and alanine transaminase enzyme activity. Lung tissue showed interstitial pneumonia and mononuclear cells, interseptal oedema, hyperplasia, and hypertrophy of the bronchiolar epithelial cells. DENV-2 led to a transient inflammatory process, but caused focal alterations of the blood-exchange barrier. Viremia was observed from 2nd to 11th day p.i. by isolation of DENV-2 in C6/36 mosquito cell line inoculated with the supernatant of macerated liver, lung, kidney, and cerebellum tissues of the infected mice.

  20. Specific-pathogen-free pigs as an animal model for studying Chlamydia trachomatis genital infection.

    Science.gov (United States)

    Vanrompay, Daisy; Hoang, Thi Q T; De Vos, Liselotte; Verminnen, Kristel; Harkinezhad, Taher; Chiers, Koen; Morré, Servaas A; Cox, Eric

    2005-12-01

    The purpose of the present study was to evaluate pigs as a large-animal model for female genital infection with two Chlamydia trachomatis human serovar E strains. Sixteen-week-old specific-pathogen-free female pigs (gilts) were intravaginally infected with the trachoma type E reference strain Bour or the urogenital serovar E strain 468. Several conclusions can be drawn from our findings on the pathogenicity of a primary C. trachomatis genital infection in gilts. First of all, we demonstrated that the serovar E strains Bour and 468 could ascend in the genital tract of gilts. The serovar E strains could replicate in the superficial columnar cervical epithelium and in the superficial epithelial layer of the uterus, which are known to be the specific target sites for a C. trachomatis genital infection in women. Second, inflammation and pathology occurred at the replication sites. Third, the organisms could trigger a humoral immune response, as demonstrated by the presence of immunoglobulin M (IgM), IgG, and IgA in both serum and genital secretion samples. Our findings imply that the pig model might be useful for studying the pathology, pathogenesis, and immune response to a C. trachomatis infection of the genital system.

  1. Predictive Virtual Infection Modeling of Fungal Immune Evasion in Human Whole Blood.

    Science.gov (United States)

    Prauße, Maria T E; Lehnert, Teresa; Timme, Sandra; Hünniger, Kerstin; Leonhardt, Ines; Kurzai, Oliver; Figge, Marc Thilo

    2018-01-01

    Bloodstream infections by the human-pathogenic fungi Candida albicans and Candida glabrata increasingly occur in hospitalized patients and are associated with high mortality rates. The early immune response against these fungi in human blood comprises a concerted action of humoral and cellular components of the innate immune system. Upon entering the blood, the majority of fungal cells will be eliminated by innate immune cells, i.e., neutrophils and monocytes. However, recent studies identified a population of fungal cells that can evade the immune response and thereby may disseminate and cause organ dissemination, which is frequently observed during candidemia. In this study, we investigate the so far unresolved mechanism of fungal immune evasion in human whole blood by testing hypotheses with the help of mathematical modeling. We use a previously established state-based virtual infection model for whole-blood infection with C. albicans to quantify the immune response and identified the fungal immune-evasion mechanism. While this process was assumed to be spontaneous in the previous model, we now hypothesize that the immune-evasion process is mediated by host factors and incorporate such a mechanism in the model. In particular, we propose, based on previous studies that the fungal immune-evasion mechanism could possibly arise through modification of the fungal surface by as of yet unknown proteins that are assumed to be secreted by activated neutrophils. To validate or reject any of the immune-evasion mechanisms, we compared the simulation of both immune-evasion models for different infection scenarios, i.e., infection of whole blood with either C. albicans or C. glabrata under non-neutropenic and neutropenic conditions. We found that under non-neutropenic conditions, both immune-evasion models fit the experimental data from whole-blood infection with C. albicans and C. glabrata . However, differences between the immune-evasion models could be observed for the

  2. Predictive Virtual Infection Modeling of Fungal Immune Evasion in Human Whole Blood

    Directory of Open Access Journals (Sweden)

    Maria T. E. Prauße

    2018-03-01

    Full Text Available Bloodstream infections by the human-pathogenic fungi Candida albicans and Candida glabrata increasingly occur in hospitalized patients and are associated with high mortality rates. The early immune response against these fungi in human blood comprises a concerted action of humoral and cellular components of the innate immune system. Upon entering the blood, the majority of fungal cells will be eliminated by innate immune cells, i.e., neutrophils and monocytes. However, recent studies identified a population of fungal cells that can evade the immune response and thereby may disseminate and cause organ dissemination, which is frequently observed during candidemia. In this study, we investigate the so far unresolved mechanism of fungal immune evasion in human whole blood by testing hypotheses with the help of mathematical modeling. We use a previously established state-based virtual infection model for whole-blood infection with C. albicans to quantify the immune response and identified the fungal immune-evasion mechanism. While this process was assumed to be spontaneous in the previous model, we now hypothesize that the immune-evasion process is mediated by host factors and incorporate such a mechanism in the model. In particular, we propose, based on previous studies that the fungal immune-evasion mechanism could possibly arise through modification of the fungal surface by as of yet unknown proteins that are assumed to be secreted by activated neutrophils. To validate or reject any of the immune-evasion mechanisms, we compared the simulation of both immune-evasion models for different infection scenarios, i.e., infection of whole blood with either C. albicans or C. glabrata under non-neutropenic and neutropenic conditions. We found that under non-neutropenic conditions, both immune-evasion models fit the experimental data from whole-blood infection with C. albicans and C. glabrata. However, differences between the immune-evasion models could be

  3. Outcome prediction in a mathematical model of immune response to infection

    Science.gov (United States)

    Mai, Manuel; Wang, Kun; Kirby, Michael; Shattuck, Mark D.; O'Hern, Corey S.

    2014-03-01

    In clinical settings, it is of great importance to diagnose patients in the shortest amount of time and with the highest achievable accuracy. Current open questions concerning the modeling of the host response to infection include: How many measurements and with what frequency are needed to diagnose patients with a given accuracy? What is the effect of patient variation on the prediction accuracy? We employ machine-learning techniques to predict disease outcomes from data generated from a set of ordinary differential equations (ODE) used to model the immune response to infection. ODE models have the advantage that we can generate an unlimited amount of data, and we can easily simulate patient differences by varying model parameters. We explore the dependence of the prediction accuracy on data sets generated from the sets of ODEs as a function of the number of and spacing between measurements, number of measured variables, and the size of the patient variability.

  4. Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection Device

    Directory of Open Access Journals (Sweden)

    Susanne Johansson

    2007-01-01

    Full Text Available The route and method of immunization, as well as the cellular localization of the antigen, can influence the generation of an immune response. In general, intramuscular immunization results in Th1 responses, whereas intradermal delivery of DNA by gene gun immunization often results in more Th2 responses. Here we investigate how altering the cellular localization of the tumor antigen CEA (carcinoembryonic antigen affects the quality and amplitude of DNA vaccine-induced antibody responses in mice following intradermal delivery of DNA by a needle-free jet injection device (Biojector. CEA was expressed either in a membrane-bound form (wild-type CEA or in two truncated forms (CEA6 and CEA66 with cytoplasmic localization, where CEA66 was fused to a promiscuous T-helper epitope from tetanus toxin. Repeated intradermal immunization of BALB/c mice with DNA encoding wild-type CEA produced high antibody titers of a mixed IgG1/IgG2a ratio. In contrast, utilizing the DNA construct that resulted in intracellular targeting of CEA led to a reduced capacity to induce CEA-specific antibodies, but instead induced a Th1-biased immune response.

  5. New Paradigms for the Study of Ocular Alphaherpesvirus Infections: Insights into the Use of Non-Traditional Host Model Systems

    Directory of Open Access Journals (Sweden)

    Matthew R. Pennington

    2017-11-01

    Full Text Available Ocular herpesviruses, most notably human alphaherpesvirus 1 (HSV-1, canid alphaherpesvirus 1 (CHV-1 and felid alphaherpesvirus 1 (FHV-1, infect and cause severe disease that may lead to blindness. CHV-1 and FHV-1 have a pathogenesis and induce clinical disease in their hosts that is similar to HSV-1 ocular infections in humans, suggesting that infection of dogs and cats with CHV-1 and FHV-1, respectively, can be used as a comparative natural host model of herpesvirus-induced ocular disease. In this review, we discuss both strengths and limitations of the various available model systems to study ocular herpesvirus infection, with a focus on the use of these non-traditional virus-natural host models. Recent work has demonstrated the robustness and reproducibility of experimental ocular herpesvirus infections in dogs and cats, and, therefore, these non-traditional models can provide additional insights into the pathogenesis of ocular herpesvirus infections.

  6. An in vitro model of intestinal infection reveals a developmentally regulated transcriptome of Toxoplasma sporozoites and a NF-κB-like signature in infected host cells.

    Directory of Open Access Journals (Sweden)

    Pascale S Guiton

    Full Text Available Toxoplasmosis is a zoonotic infection affecting approximately 30% of the world's human population. After sexual reproduction in the definitive feline host, Toxoplasma oocysts, each containing 8 sporozoites, are shed into the environment where they can go on to infect humans and other warm-blooded intermediate hosts. Here, we use an in vitro model to assess host transcriptomic changes that occur in the earliest stages of such infections. We show that infection of rat intestinal epithelial cells with mature sporozoites primarily results in higher expression of genes associated with Tumor Necrosis Factor alpha (TNFα signaling via NF-κB. Furthermore, we find that, consistent with their biology, these mature, invaded sporozoites display a transcriptome intermediate between the previously reported day 10 oocysts and that of their tachyzoite counterparts. Thus, this study uncovers novel host and pathogen factors that may be critical for the establishment of a successful intracellular niche following sporozoite-initiated infection.

  7. A Novel 3D Skin Explant Model to Study Anaerobic Bacterial Infection

    OpenAIRE

    Maboni, Grazieli; Davenport, Rebecca; Sessford, Kate; Baiker, Kerstin; Jensen, Tim K.; Blanchard, Adam M.; Wattegedera, Sean; Entrican, Gary; Tötemeyer, Sabine

    2017-01-01

    Skin infection studies are often limited by financial and ethical constraints, and alternatives, such as monolayer cell culture, do not reflect many cellular processes limiting their application. For a more functional replacement, 3D skin culture models offer many advantages such as the maintenance of the tissue structure and the cell types present in the host environment. A 3D skin culture model can be set up using tissues acquired from surgical procedures or post slaughter, making it a cost...

  8. Modeling Klebsiella pneumoniae Pathogenesis by Infection of the Wax Moth Galleria mellonella

    Science.gov (United States)

    Insua, José Luis; Llobet, Enrique; Moranta, David; Pérez-Gutiérrez, Camino; Tomás, Anna; Garmendia, Junkal

    2013-01-01

    The implementation of infection models that approximate human disease is essential for understanding pathogenesis at the molecular level and for testing new therapies before they are entered into clinical stages. Insects are increasingly being used as surrogate hosts because they share, with mammals, essential aspects of the innate immune response to infections. We examined whether the larva of the wax moth Galleria mellonella could be used as a host model to conceptually approximate Klebsiella pneumoniae-triggered pneumonia. We report that the G. mellonella model is capable of distinguishing between pathogenic and nonpathogenic Klebsiella strains. Moreover, K. pneumoniae infection of G. mellonella models some of the known features of Klebsiella-induced pneumonia, i.e., cell death associated with bacterial replication, avoidance of phagocytosis by phagocytes, and the attenuation of host defense responses, chiefly the production of antimicrobial factors. Similar to the case for the mouse pneumonia model, activation of innate responses improved G. mellonella survival against subsequent Klebsiella challenge. Virulence factors necessary in the mouse pneumonia model were also implicated in the Galleria model. We found that mutants lacking capsule polysaccharide, lipid A decorations, or the outer membrane proteins OmpA and OmpK36 were attenuated in Galleria. All mutants activated G. mellonella defensive responses. The Galleria model also allowed us to monitor Klebsiella gene expression. The expression levels of cps and the loci implicated in lipid A remodeling peaked during the first hours postinfection, in a PhoPQ- and PmrAB-governed process. Taken together, these results support the utility of G. mellonella as a surrogate host for assessing infections with K. pneumoniae. PMID:23836821

  9. A nonstandard finite difference scheme for a basic model of cellular immune response to viral infection

    Science.gov (United States)

    Korpusik, Adam

    2017-02-01

    We present a nonstandard finite difference scheme for a basic model of cellular immune response to viral infection. The main advantage of this approach is that it preserves the essential qualitative features of the original continuous model (non-negativity and boundedness of the solution, equilibria and their stability conditions), while being easy to implement. All of the qualitative features are preserved independently of the chosen step-size. Numerical simulations of our approach and comparison with other conventional simulation methods are presented.

  10. Cosmeceutical effect of ethyl acetate fraction of Kombucha tea by intradermal administration in the skin of aged mice.

    Science.gov (United States)

    Pakravan, Nafiseh; Mahmoudi, Elaheh; Hashemi, Seyed-Ali; Kamali, Jamal; Hajiaghayi, Reza; Rahimzadeh, Mitra; Mahmoodi, Vajiheh

    2017-11-19

    Natural ingredients have been always an interesting approach to prolong youthful appearance of skin. One of the natural compounds is Kombucha tea (KT), which has been mainly used as an energy drink in Asian countries for a long time. Previous reports indicated that it has pharmaceutical and favorable wound repairing effects. The beneficial properties of KT are thought to be mainly due to the presence of fermentation products such as flavonoids and other polyphenols with inhibition of hydrolytic and oxidative enzymes and anti-inflammatory effects. These properties prompted us to study the anti-aging potential of KT and investigate its effective fraction in aged mice, METHODS: Kombucha tea was fractionated into chloroform, butanol, and ethyl acetate, and flavonoid content was determined. Young and old mice were used as control. KT ethyl acetate fraction (KEAf), which had the highest flavonoid content, was intradermally administered to old mice. Administration of KEAf significantly increased the collagen content, NAD + /NADH level, and concomitantly improved skin connective tissue abnormalities in the aged skin. No sensitivity or irritation was observed. This finding suggested that KEAf can be a suitable candidate as a cosmetic product to improve aging-related skin abnormalities and regeneration of aged skin. © 2017 Wiley Periodicals, Inc.

  11. Examining the virulence of Candida albicans transcription factor mutants using Galleria mellonella and mouse infection models

    Directory of Open Access Journals (Sweden)

    Sara eAmorim-Vaz

    2015-05-01

    Full Text Available The aim of the present study was to identify C. albicans transcription factors (TF involved in virulence. Although mice are considered the gold-standard model to study fungal virulence, mini-host infection models have been increasingly used. Here, barcoded TF mutants were first screened in mice by pools of strains and fungal burdens quantified in kidneys. Mutants of unannotated genes which generated a kidney fungal burden significantly different from that of wild-type were selected and individually examined in G. mellonella. In addition, mutants that could not be detected in mice were also tested in G. mellonella. Only 25 % of these mutants displayed matching phenotypes in both hosts, highlighting a significant discrepancy between the two models. To address the basis of this difference (pool or host effects, a set of 19 mutants tested in G. mellonella were also injected individually into mice. Matching fungal burden phenotypes were observed in 50 % of the cases, highlighting the bias due to host effects. In contrast, 33.4 % concordance was observed between pool and single strain infections in mice, thereby highlighting the bias introduced by the pool effect. After filtering the results obtained from the two infection models, mutants for MBF1 and ZCF6 were selected. Independent marker-free mutants were subsequently tested in both hosts to validate previous results. The MBF1 mutant showed impaired infection in both models, while the ZCF6 mutant was only significant in mice infections. The two mutants showed no obvious in vitro phenotypes compared with the wild-type, indicating that these genes might be specifically involved in in vivo adaptation.

  12. Defining New Therapeutics Using a More Immunocompetent Mouse Model of Antibody-Enhanced Dengue Virus Infection.

    Science.gov (United States)

    Pinto, Amelia K; Brien, James D; Lam, Chia-Ying Kao; Johnson, Syd; Chiang, Cindy; Hiscott, John; Sarathy, Vanessa V; Barrett, Alan D; Shresta, Sujan; Diamond, Michael S

    2015-09-15

    With over 3.5 billion people at risk and approximately 390 million human infections per year, dengue virus (DENV) disease strains health care resources worldwide. Previously, we and others established models for DENV pathogenesis in mice that completely lack subunits of the receptors (Ifnar and Ifngr) for type I and type II interferon (IFN) signaling; however, the utility of these models is limited by the pleotropic effect of these cytokines on innate and adaptive immune system development and function. Here, we demonstrate that the specific deletion of Ifnar expression on subsets of murine myeloid cells (LysM Cre(+) Ifnar(flox/flox) [denoted as Ifnar(f/f) herein]) resulted in enhanced DENV replication in vivo. The administration of subneutralizing amounts of cross-reactive anti-DENV monoclonal antibodies to LysM Cre(+) Ifnar(f/f) mice prior to infection with DENV serotype 2 or 3 resulted in antibody-dependent enhancement (ADE) of infection with many of the characteristics associated with severe DENV disease in humans, including plasma leakage, hypercytokinemia, liver injury, hemoconcentration, and thrombocytopenia. Notably, the pathogenesis of severe DENV-2 or DENV-3 infection in LysM Cre(+) Ifnar(f/f) mice was blocked by pre- or postexposure administration of a bispecific dual-affinity retargeting molecule (DART) or an optimized RIG-I receptor agonist that stimulates innate immune responses. Our findings establish a more immunocompetent animal model of ADE of infection with multiple DENV serotypes in which disease is inhibited by treatment with broad-spectrum antibody derivatives or innate immune stimulatory agents. Although dengue virus (DENV) infects hundreds of millions of people annually and results in morbidity and mortality on a global scale, there are no approved antiviral treatments or vaccines. Part of the difficulty in evaluating therapeutic candidates is the lack of small animal models that are permissive to DENV and recapitulate the clinical features

  13. Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection.

    Science.gov (United States)

    Cui, Liang; Hou, Jue; Fang, Jinling; Lee, Yie Hou; Costa, Vivian Vasconcelos; Wong, Lan Hiong; Chen, Qingfeng; Ooi, Eng Eong; Tannenbaum, Steven R; Chen, Jianzhu; Ong, Choon Nam

    2017-07-15

    Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted mass spectrometry-based serum metabolic profiling from a model using humanized mice (humice) with DENV serotype 2 infection at 0, 3, 7, 14, and 28 days postinfection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acids and derivatives, free fatty acids, and bile acid. These metabolites showed a reversible-change trend-most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that the metabolites might serve as prognostic markers of the disease in humice. The major perturbed metabolic pathways included purine and pyrimidine metabolism, fatty acid β-oxidation, phospholipid catabolism, arachidonic acid and linoleic acid metabolism, sphingolipid metabolism, tryptophan metabolism, phenylalanine metabolism, lysine biosynthesis and degradation, and bile acid biosynthesis. Most of these disturbed pathways are similar to our previous metabolomics findings in a longitudinal cohort of adult human dengue patients across different infection stages. Our analyses revealed the commonalities of host responses to DENV infection between humice and humans and suggested that humice could be a useful small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics. IMPORTANCE Dengue virus is the most widespread arbovirus, causing an estimated 390 million dengue infections worldwide every year. There is currently no effective treatment for the disease, and the lack of an appropriate small-animal model of dengue infection has greatly

  14. Evaluation of MBEC™-HTP biofilm model for studies of implant associated infections.

    Science.gov (United States)

    Coraça-Hubér, Debora C; Fille, Manfred; Hausdorfer, Johann; Pfaller, Kristian; Nogler, Michael

    2012-07-01

    The bacteria in implant-related infections can evade host defenses by forming biofilms. The more we understand biofilm behavior, the better we can fight against then clinically. In vitro models for biofilms allow tests simulating in vivo conditions. In this study we evaluated the Minimum Biofilm Eradication Concentration-High Throughput Plates (MBEC™-HTP) as biofilm in vitro model for studies of implant associated infections. Staphylococcus aureus and Staphylococcus epidermidis biofilms were grown on MBEC™-HTP. To ensure the biofilm formation, antibiotic susceptibility tests and scanning electron microscopy (SEM) was carried out. Susceptibility tests were carried out using gentamicin, vancomycin, rifampicin, fosfomycin, clindamycin, and linezolid. Colony forming units counting were carried out. Minimal inhibitory concentration (MIC) and biofilm inhibitory concentration (BIC) were estimated. The CFU counting showed potency of rifampicin and daptomycin against S. epidermidis biofilms and rifampicin against S. aureus biofilms. SEM images showed proteic material in contact with cells. The differences between BIC and MIC demonstrated the biofilm formation as well as the SEM images. Rifampicin and daptomycin are good choices against biofilm related infections. Moreover, after suggested modifications, the model used in this study is eligible to further studies of implant associated infections. Copyright © 2012 Orthopaedic Research Society.

  15. Risk factors for failure to detect bovine tuberculosis in cattle from infected herds across Northern Ireland (2004-2010).

    Science.gov (United States)

    Lahuerta-Marin, Angela; McNair, James; Skuce, Robin; McBride, Stewart; Allen, Michelle; Strain, Sam A J; Menzies, Fraser D; McDowell, Stanley J W; Byrne, Andrew W

    2016-08-01

    Correctly identifying animals that are truly infected with a pathogen using ante-mortem tests is the cornerstone of any disease eradication programme. Failure to identify all infected animals will impede the progress towards controlling and eradicating disease and may also have unforeseen consequences when specific prevention measures are in place to avoid animal-to-animal transmission. In the case of bovine tuberculosis (bTB), the screening ante-mortem test, the Single Comparative Intradermal Tuberculin Test (SCITT), can exhibit moderate sensitivity which can result in a "hidden burden" of infection residing within the population. Using an animal-level dataset relating to the disclosure of infected cattle with Mycobacterium bovis, the causative agent of bTB within infected herds in Northern Ireland, we investigated what factors influenced the probability of an animal being a false-negative when truly infected (using post-mortem (PM) microbiological culture confirmation results to assess infection status). We found that different risk factors affected the probability of a test-negative outcome on infected animals depending on the ante-mortem test or their combination (SICTT and/or interferon gamma (IFN-ɣ) testing). Using multivariable models, SCITT disclosure performance varied significantly by age, location (region), and production type. The IFN-ɣ tests were significantly affected by region or season, but these effects depended on the cut-off used during interpretation of the test which affected the tests characteristics. Parallel use of SCITT and IFN-ɣ tests resulted in the least number of false-negatives, and their disclosure was affected by season and age-class. Understanding the factors that lead to the non-disclosure of infected animals is essential to optimise large-scale bTB disease eradication programmes. Copyright © 2016. Published by Elsevier Ltd.

  16. Inactivation of the CovR/S Virulence Regulator Impairs Infection in an Improved Murine Model of Streptococcus pyogenes Naso-Pharyngeal Infection

    Science.gov (United States)

    Alam, Faraz M.; Turner, Claire E.; Smith, Ken; Wiles, Siouxsie; Sriskandan, Shiranee

    2013-01-01

    Streptococcus pyogenes is a leading cause of pharyngeal infection, with an estimated 616 million cases per year. The human nasopharynx represents the major reservoir for all S. pyogenes infection, including severe invasive disease. To investigate bacterial and host factors that influence S. pyogenes infection, we have devised an improved murine model of nasopharyngeal colonization, with an optimized dosing volume to avoid fulminant infections and a sensitive host strain. In addition we have utilized a refined technique for longitudinal monitoring of bacterial burden that is non-invasive thereby reducing the numbers of animals required. The model was used to demonstrate that the two component regulatory system, CovR/S, is required for optimum infection and transmission from the nasopharynx. There is a fitness cost conferred by covR/S mutation that is specific to the nasopharynx. This may explain why S. pyogenes with altered covR/S have not become prevalent in community infections despite possessing a selective advantage in invasive infection. PMID:23637876

  17. Alternative states and population crashes in a resource-susceptible-infected model for planktonic parasites and hosts

    NARCIS (Netherlands)

    Gerla, D.J.; Gsell, A.S.; Kooi, B.W.; Ibelings, B.W.; Donk, van E.; Mooij, W.M.

    2013-01-01

    1. Despite the strong impact parasites can have, only few models of phytoplankton ecology or aquatic food webs have specifically included parasitism. 2. Here, we provide a susceptible-infected model for a diatom-chytrid hostparasite system that explicitly includes nutrients, infected and uninfected

  18. Predictive computational modeling of the mucosal immune responses during Helicobacter pylori infection.

    Directory of Open Access Journals (Sweden)

    Adria Carbo

    Full Text Available T helper (Th cells play a major role in the immune response and pathology at the gastric mucosa during Helicobacter pylori infection. There is a limited mechanistic understanding regarding the contributions of CD4+ T cell subsets to gastritis development during H. pylori colonization. We used two computational approaches: ordinary differential equation (ODE-based and agent-based modeling (ABM to study the mechanisms underlying cellular immune responses to H. pylori and how CD4+ T cell subsets influenced initiation, progression and outcome of disease. To calibrate the model, in vivo experimentation was performed by infecting C57BL/6 mice intragastrically with H. pylori and assaying immune cell subsets in the stomach and gastric lymph nodes (GLN on days 0, 7, 14, 30 and 60 post-infection. Our computational model reproduced the dynamics of effector and regulatory pathways in the gastric lamina propria (LP in silico. Simulation results show the induction of a Th17 response and a dominant Th1 response, together with a regulatory response characterized by high levels of mucosal Treg cells. We also investigated the potential role of peroxisome proliferator-activated receptor γ (PPARγ activation on the modulation of host responses to H. pylori by using loss-of-function approaches. Specifically, in silico results showed a predominance of Th1 and Th17 cells in the stomach of the cell-specific PPARγ knockout system when compared to the wild-type simulation. Spatio-temporal, object-oriented ABM approaches suggested similar dynamics in induction of host responses showing analogous T cell distributions to ODE modeling and facilitated tracking lesion formation. In addition, sensitivity analysis predicted a crucial contribution of Th1 and Th17 effector responses as mediators of histopathological changes in the gastric mucosa during chronic stages of infection, which were experimentally validated in mice. These integrated immunoinformatics approaches

  19. Young Sprague Dawley rats infected by Plasmodium berghei: A relevant experimental model to study cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Sokhna Keita Alassane

    Full Text Available Cerebral malaria (CM is the most severe manifestation of human malaria yet is still poorly understood. Mouse models have been developed to address the subject. However, their relevance to mimic human pathogenesis is largely debated. Here we study an alternative cerebral malaria model with an experimental Plasmodium berghei Keyberg 173 (K173 infection in Sprague Dawley rats. As in Human, not all infected subjects showed cerebral malaria, with 45% of the rats exhibiting Experimental Cerebral Malaria (ECM symptoms while the majority (55% of the remaining rats developed severe anemia and hyperparasitemia (NoECM. These results allow, within the same population, a comparison of the noxious effects of the infection between ECM and severe malaria without ECM. Among the ECM rats, 77.8% died between day 5 and day 12 post-infection, while the remaining rats were spontaneously cured of neurological signs within 24-48 hours. The clinical ECM signs observed were paresis quickly evolving to limb paralysis, global paralysis associated with respiratory distress, and coma. The red blood cell (RBC count remained normal but a drastic decrease of platelet count and an increase of white blood cell numbers were noted. ECM rats also showed a decrease of glucose and total CO2 levels and an increase of creatinine levels compared to control rats or rats with no ECM. Assessment of the blood-brain barrier revealed loss of integrity, and interestingly histopathological analysis highlighted cyto-adherence and sequestration of infected RBCs in brain vessels from ECM rats only. Overall, this ECM rat model showed numerous clinical and histopathological features similar to Human CM and appears to be a promising model to achieve further understanding the CM pathophysiology in Humans and to evaluate the activity of specific antimalarial drugs in avoiding/limiting cerebral damages from malaria.

  20. Chimeric mouse model for the infection of hepatitis B and C viruses.

    Directory of Open Access Journals (Sweden)

    Abeba Tesfaye

    Full Text Available While the chimpanzee remains the only animal that closely models human hepatitis C virus (HCV infection, transgenic and immunodeficient mice in which human liver can be engrafted serve as a partial solution to the need for a small animal model for HCV infection. The established system that was based on mice carrying a transgene for urokinase-type plasminogen activator (uPA gene under the control of the human albumin promoter has proved to be useful for studies of virus infectivity and for testing antiviral drug agents. However, the current Alb-uPA transgenic model with a humanized liver has practical limitations due to the inability to maintain non-engrafted mice as dizygotes for the transgene, poor engraftment of hemizygotes, high neonatal and experimental death rates of dizygous mice and a very short time window for hepatocyte engraftment. To improve the model, we crossed transgenic mice carrying the uPA gene driven by the major urinary protein promoter onto a SCID/Beige background (MUP-uPA SCID/Bg. These transgenic mice are healthy relative to Alb-uPA mice and provide a long window from about age 4 to 12 months for engraftment with human hepatocytes and infection with hepatitis C or hepatitis B (HBV viruses. We have demonstrated engraftment of human hepatocytes by immunohistochemistry staining for human albumin (30-80% engraftment and observed a correlation between the number of human hepatocytes inoculated and the level of the concentration of human albumin in the serum. We have shown that these mice support the replication of both HBV and all six major HCV genotypes. Using HBV and HCV inocula that had been previously tittered in chimpanzees, we showed that the mice had approximately the same sensitivity for infection as chimpanzees. These mice should be useful for isolating non-cell culture adapted viruses as well as testing of antiviral drugs, antibody neutralization studies and examination of phenotypic changes in viral mutants.

  1. Salmonella infections modelling in Mississippi using neural network and geographical information system (GIS).

    Science.gov (United States)

    Akil, Luma; Ahmad, H Anwar

    2016-03-03

    Mississippi (MS) is one of the southern states with high rates of foodborne infections. The objectives of this paper are to determine the extent of Salmonella and Escherichia coli infections in MS, and determine the Salmonella infections correlation with socioeconomic status using geographical information system (GIS) and neural network models. In this study, the relevant updated data of foodborne illness for southern states, from 2002 to 2011, were collected and used in the GIS and neural networks models. Data were collected from the Centers for Disease Control and Prevention (CDC), MS state Department of Health and the other states department of health. The correlation between low socioeconomic status and Salmonella infections were determined using models created by several software packages, including SAS, ArcGIS @RISK and NeuroShell. Results of this study showed a significant increase in Salmonella outbreaks in MS during the study period, with highest rates in 2011 (47.84 ± 24.41 cases/100,000; pGIS maps of Salmonella outbreaks in MS in 2010 and 2011 showed the districts with higher rates of Salmonella. Regression analysis and neural network models showed a moderate correlation between cases of Salmonella infections and low socioeconomic factors. Poverty was shown to have a negative correlation with Salmonella outbreaks (R(2)=0.152, p<0.05). Geographic location besides socioeconomic status may contribute to the high rates of Salmonella outbreaks in MS. Understanding the geographical and economic relationship with infectious diseases will help to determine effective methods to reduce outbreaks within low socioeconomic status communities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Efficacy of cocktail phage therapy in treating Vibrio cholerae infection in rabbit model.

    Science.gov (United States)

    Jaiswal, Abhishek; Koley, Hemanta; Ghosh, Amit; Palit, Anup; Sarkar, Banwarilal

    2013-02-01

    Ability of a cocktail of five lytic vibriophages to combatting Vibrio cholerae O1 infection in rabbit model was examined. In one group, rabbits were administered 1 × 10(8) plaque forming unit of phage cocktail 6 and 12 h prior to the administration of V. cholerae O1, while in the other group, same procedure was applied 6 and 12 h post infection. It was observed that oral administration of the phage cocktail after oral bacterial challenge lowered the shedding of bacteria significantly (p phage treatment prior to bacterial challenge had no such effect (p > 0.05). Results suggest that oral administration of phage subsequent to V. cholerae challenge could provide a possible means of combatting V. cholerae infection. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  3. A mouse model of inflammatory root resorption induced by pulpal infection.

    Science.gov (United States)

    Balto, Khaled; White, Robert; Mueller, Ralph; Stashenko, Philip

    2002-04-01

    The present study was undertaken to determine the frequency and extent of apical root resorption associated with induced periradicular lesions in mice. Bone and root resorption was quantified by using two- and three-dimensional micro-computed tomography (mu-CT) in the lower first molars of mice subjected to pulp exposure and infection. mu-CT measurements showed significant apical resorption in exposed and infected teeth, resulting in an average distal root shortening of 12.7% (P staining showed the presence of bacteria in dentinal tubules adjacent to resorbed cementum. Apical root resorption is a prominent and consistent finding associated with periradicular infection in the mouse. This species represents a convenient model for studying the pathogenesis of inflammatory root resorption in vivo.

  4. Synthesis and biodistribution of 99mTc-Vancomycin in a model of bacterial infection

    International Nuclear Information System (INIS)

    Roohi, S.; Mushtaq, A.; Malik, S.A.

    2005-01-01

    Vancomycin Hydrochloride is an antibiotic produced by the growth of certain strains of Streptomyces orientalis. As vancomycin hydrochloride is poorly absorbed after oral administration; it is given intravenously for therapy of systemic infections. Vancomycin was labeled with technetium-99m pertechnetate using SnCl 2 . 2H 2 O as reducing agent. The labeling efficiency depends on ligand/reductant ratio, pH, and volume of reaction mixture. Radiochemical purity and stability of 99m Tc-Vancomycin was determined by thin layer chromatography. Biodistribution studies of 99m Tc-Vancomycin were performed in a model of bacterial infection in Sprague-Dawley rats. A significantly higher accumulation of 99m Tc-Vancomycin was seen at sites of S. aureus infected animals. Whereas uptake of 99m Tc-Vancomycin in turpentine inflamed rats were quite low. (orig.)

  5. Efficacy of telavancin, a lipoglycopeptide antibiotic, in experimental models of Gram-positive infection.

    Science.gov (United States)

    Hegde, Sharath S; Janc, James W

    2014-12-01

    Telavancin is a parenteral lipoglycopeptide antibiotic with a dual mechanism of action contributing to bactericidal activity against multidrug-resistant Gram-positive pathogens. It has been approved for the treatment of complicated skin and skin structure infections due to susceptible Gram-positive bacteria and hospital-acquired/ventilator-associated bacterial pneumonia due to Staphylococcus aureus when other alternatives are unsuitable. Telavancin has been demonstrated to be efficacious in multiple animal models of soft tissue, cardiac, systemic, lung, bone, brain and device-associated infections involving clinically relevant Gram-positive pathogens, including methicillin-resistant S. aureus, glycopeptide-intermediate S. aureus, heterogeneous vancomycin-intermediate S. aureus and daptomycin non-susceptible methicillin-resistant S. aureus. The AUC0-24h/MIC ratio is the primary pharmacodynamically-linked pharmacokinetic parameter. The preclinical data for telavancin supports further investigative clinical evaluation of its efficacy in additional serious infections caused by susceptible Gram-positive pathogens.

  6. In Vitro Osteoblast Model for Bone Wound Infections and Antimicrobial Therapy

    Science.gov (United States)

    2013-01-01

    study. The 3‐D osteoblast cultures would  then be infected with clinical isolates of multidrug resistant  Acinetobacter   baumannii  (AB), Klebsiella...completed successfully to establish the model, and  infections were performed with clinical isolates of multidrug resistant  Acinetobacter   baumannii ...isolates of MDR  Acinetobacter   baumannii , Pseudomonas aeruginosa, and Klebsiella pneumoniae  were obtained from WRAMC. For infections, bacterial cultures

  7. Synthesis and biodistribution of {sup 99m}Tc-Vancomycin in a model of bacterial infection

    Energy Technology Data Exchange (ETDEWEB)

    Roohi, S.; Mushtaq, A. [Isotope Production Div., Pakistan Inst. of Nuclear Science and Technology, Islamabad (Pakistan); Malik, S.A. [Dept. of Biological Sciences, Quaid-e-Azam Univ., Islamabad (Pakistan)

    2005-07-01

    Vancomycin Hydrochloride is an antibiotic produced by the growth of certain strains of Streptomyces orientalis. As vancomycin hydrochloride is poorly absorbed after oral administration; it is given intravenously for therapy of systemic infections. Vancomycin was labeled with technetium-99m pertechnetate using SnCl{sub 2} . 2H{sub 2}O as reducing agent. The labeling efficiency depends on ligand/reductant ratio, pH, and volume of reaction mixture. Radiochemical purity and stability of {sup 99m}Tc-Vancomycin was determined by thin layer chromatography. Biodistribution studies of {sup 99m}Tc-Vancomycin were performed in a model of bacterial infection in Sprague-Dawley rats. A significantly higher accumulation of {sup 99m}Tc-Vancomycin was seen at sites of S. aureus infected animals. Whereas uptake of {sup 99m}Tc-Vancomycin in turpentine inflamed rats were quite low. (orig.)

  8. Modelling borderline and mild dysplasia associated with HPV 6 and 11 infection.

    Science.gov (United States)

    Chapman, Ruth; Soldan, Kate; Jit, Mark

    2011-04-05

    Low risk HPV types 6/11 are responsible for some low-grade cytological abnormalities. Most economic analyses of HPV vaccination have estimated the additional benefit of HPV 6/11 protection by the quadrivalent vaccine, over the bivalent, based on reduction of genital warts but have not included reduction in repeat smears and colposcopies due to low-grade abnormalities. We investigate the contribution of HPV types 6/11 to abnormal smears and associated costs in England. The risk of borderline or mild dysplasia due to HPV 6/11 infection was estimated from a study of type-specific HPV DNA in cervical screening specimens collected throughout England. A Markov model representing 10 million women with HPV 6/11 or with no HPV infection from 24 to 64 years was developed to estimate the number of abnormal smears, subsequent repeat smears and colposcopies due to HPV 6/11 associated with borderline or mild dysplasia. Fitting was achieved by varying the force of infection, probability of borderline or mild dysplasia if HPV-uninfected or infected with HPV 6/11 and the duration of infection. The relative risks of borderline or mild dysplasia when infected with HPV 6/11 compared to not being HPV infected were 6.32 (95% credible interval 1.56-25.6) and 17.5 (1.02-300) respectively. Using best fitting parameters we find the costs incurred are between £170 and £195 per abnormal smear due to infection with HPV 6/11. In England, the impact of cytological abnormalities due to HPV 6/11 is relatively small, but not negligible. A vaccine that protects against HPV 6/11 infections could reduce costs associated with borderline and mild dysplasia, and associated colposcopies. These benefits should be considered when formulating immunisation policy, if possible. Smears and colposcopies in those uninfected with HPV far outnumber those in women infected with HPV 6/11. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Impacts of allergic airway inflammation on lung pathology in a mouse model of influenza A virus infection.

    Science.gov (United States)

    Kawaguchi, Akira; Suzuki, Tadaki; Ohara, Yuki; Takahashi, Kenta; Sato, Yuko; Ainai, Akira; Nagata, Noriyo; Tashiro, Masato; Hasegawa, Hideki

    2017-01-01

    Influenza A virus is the respiratory pathogen responsible for influenza. Infection by the 2009 pandemic influenza A (H1N1) virus caused severe lower airway inflammation and pneumonia. Asthma is a chronic inflammatory disorder of the airways that affects the entire brachial tree, and was one of the commonest underlying medical conditions among patients hospitalized with the 2009 pandemic influenza virus infection. Although respiratory virus infections are the major causes of asthma exacerbation, the mechanism by which influenza exacerbates asthma is poorly understood. Animal models of disease comorbidity are crucial to understanding host-pathogen interactions and elucidating complex pathologies. Existing murine models of influenza virus infection in asthmatics show that asthmatic mice are highly resistant to influenza virus infection, which contradicts clinical observations in humans. Here, we developed a murine model of influenza virus/asthma comorbidity using NC/Nga mice, which are highly sensitive to allergic reactions such as atopic dermatitis and allergic airway inflammation. This model was then used to examine the impact of allergic airway inflammation on lung pathology in the 2009 pandemic influenza virus infected mice. The results showed that induction of acute allergic airway inflammation in pre-existing influenza virus infection had additive effects on exacerbation of lung pathology, which mirrors findings in human epidemiological studies. In contrast, pre-existing allergic airway inflammation protected from subsequent influenza virus infection, which was compatible with those of previous murine models of influenza virus infection in asthmatic mice. These variable outcomes of this murine model indicate that the temporal relation between allergic airway inflammation and influenza virus infection might play a critical role in asthma and influenza comorbidity. Thus, this murine model will further our understanding of how influenza virus infection affects an

  10. Cyclic cidofovir (cHPMPC prevents congenital cytomegalovirus infection in a guinea pig model

    Directory of Open Access Journals (Sweden)

    McGregor Alistair

    2006-03-01

    Full Text Available Abstract Background Congenital cytomegalovirus (CMV infection is a major public health problem. Antiviral therapies administered during pregnancy might prevent vertical CMV transmission and disease in newborns, but these agents have not been evaluated in clinical trials. The guinea pig model of congenital CMV infection was therefore used to test the hypothesis that antiviral therapy, using the agent agent cyclic cidofovir (cHPMPC, could prevent congenital CMV infection. Results Pregnant outbred Hartley guinea pigs were challenged in the early-third trimester with guinea pig CMV (GPCMV and treated with placebo, or the antiviral agent, cyclic cidofovir. To optimize detection of vertical infection, an enhanced green fluorescent protein (eGFP-tagged virus was employed. Compared to placebo, cyclic cidofovir-treated dams and pups had reduced mortality following GPCMV challenge. The magnitude of GPCMV-induced maternal and fetal mortality in this study was reduced from 5/25 animals in the placebo group to 0/21 animals in the treatment group (p = 0.05, Fisher's exact test. By viral culture assay, antiviral therapy was found to completely prevent GPCMV transmission to the fetus. In control pups, 5/19 (26% were culture-positive for GPCMV, compared to 0/16 of pups in the cyclic cidofovir treatment group (p Conclusion Antiviral therapy with cyclic cidofovir improves pregnancy outcomes in guinea pigs, and eliminates congenital CMV infection, following viral challenge in the third trimester. This study also demonstrated that an eGFP-tagged recombinant virus, with the reporter gene inserted into a dispensable region of the viral genome, retained virulence, including the potential for congenital transmission, facilitating tissue culture-based detection of congenital infection. These observations provide support for clinical trials of antivirals for reduction of congenital CMV infection.

  11. Modelling the geographical distribution of soil-transmitted helminth infections in Bolivia.

    Science.gov (United States)

    Chammartin, Frédérique; Scholte, Ronaldo G C; Malone, John B; Bavia, Mara E; Nieto, Prixia; Utzinger, Jürg; Vounatsou, Penelope

    2013-05-25

    The prevalence of infection with the three common soil-transmitted helminths (i.e. Ascaris lumbricoides, Trichuris trichiura, and hookworm) in Bolivia is among the highest in Latin America. However, the spatial distribution and burden of soil-transmitted helminthiasis are poorly documented. We analysed historical survey data using Bayesian geostatistical models to identify determinants of the distribution of soil-transmitted helminth infections, predict the geographical distribution of infection risk, and assess treatment needs and costs in the frame of preventive chemotherapy. Rigorous geostatistical variable selection identified the most important predictors of A. lumbricoides, T. trichiura, and hookworm transmission. Results show that precipitation during the wettest quarter above 400 mm favours the distribution of A. lumbricoides. Altitude has a negative effect on T. trichiura. Hookworm is sensitive to temperature during the coldest month. We estimate that 38.0%, 19.3%, and 11.4% of the Bolivian population is infected with A. lumbricoides, T. trichiura, and hookworm, respectively. Assuming independence of the three infections, 48.4% of the population is infected with any soil-transmitted helminth. Empirical-based estimates, according to treatment recommendations by the World Health Organization, suggest a total of 2.9 million annualised treatments for the control of soil-transmitted helminthiasis in Bolivia. We provide estimates of soil-transmitted helminth infections in Bolivia based on high-resolution spatial prediction and an innovative variable selection approach. However, the scarcity of the data suggests that a national survey is required for more accurate mapping that will govern spatial targeting of soil-transmitted helminthiasis control.

  12. Agent-Based Model to Study and Quantify the Evolution Dynamics of Android Malware Infection

    Directory of Open Access Journals (Sweden)

    Juan Alegre-Sanahuja

    2014-01-01

    Full Text Available In the last years the number of malware Apps that the users download to their devices has risen. In this paper, we propose an agent-based model to quantify the Android malware infection evolution, modeling the behavior of the users and the different markets where the users may download Apps. The model predicts the number of infected smartphones depending on the type of malware. Additionally, we will estimate the cost that the users should afford when the malware is in their devices. We will be able to analyze which part is more critical: the users, giving indiscriminate permissions to the Apps or not protecting their devices with antivirus software, or the Android platform, due to the vulnerabilities of the Android devices that permit their rooted. We focus on the community of Valencia, Spain, although the obtained results can be extrapolated to other places where the number of Android smartphones remains fairly stable.

  13. Chlamydophila abortus infection in the mouse: a useful model of the ovine disease.

    Science.gov (United States)

    Caro, M R; Buendía, A J; Del Rio, L; Ortega, N; Gallego, M C; Cuello, F; Navarro, J A; Sanchez, J; Salinas, J

    2009-03-16

    Chlamydophila (C.) abortus is an obligate intracellular bacterium able to colonize the placenta of several species of mammals, which may induce abortion in the last third of pregnancy. The infection affects mainly small ruminants resulting in major economic losses in farming industries worldwide. Furthermore, its zoonotic risk has been reported in pregnant farmers or abattoir workers. Mouse models have been widely used to study both the pathology of the disease and the role of immune cells in controlling infection. Moreover, this animal experimental model has been considered a useful tool to evaluate new vaccine candidates and adjuvants that could prevent abortion and reduce fetal death. Future studies using these models will provide and reveal information about the precise mechanisms in the immune response against C. abortus and will increase the knowledge about poorly understood issues such as chlamydial persistence.

  14. Building predictive models for MERS-CoV infections using data mining techniques.

    Science.gov (United States)

    Al-Turaiki, Isra; Alshahrani, Mona; Almutairi, Tahani

    Recently, the outbreak of MERS-CoV infections caused worldwide attention to Saudi Arabia. The novel virus belongs to the coronaviruses family, which is responsible for causing mild to moderate colds. The control and command center of Saudi Ministry of Health issues a daily report on MERS-CoV infection cases. The infection with MERS-CoV can lead to fatal complications, however little information is known about this novel virus. In this paper, we apply two data mining techniques in order to better understand the stability and the possibility of recovery from MERS-CoV infections. The Naive Bayes classifier and J48 decision tree algorithm were used to build our models. The dataset used consists of 1082 records of cases reported between 2013 and 2015. In order to build our prediction models, we split the dataset into two groups. The first group combined recovery and death records. A new attribute was created to indicate the record type, such that the dataset can be used to predict the recovery from MERS-CoV. The second group contained the new case records to be used to predict the stability of the infection based on the current status attribute. The resulting recovery models indicate that healthcare workers are more likely to survive. This could be due to the vaccinations that healthcare workers are required to get on regular basis. As for the stability models using J48, two attributes were found to be important for predicting stability: symptomatic and age. Old patients are at high risk of developing MERS-CoV complications. Finally, the performance of all the models was evaluated using three measures: accuracy, precision, and recall. In general, the accuracy of the models is between 53.6% and 71.58%. We believe that the performance of the prediction models can be enhanced with the use of more patient data. As future work, we plan to directly contact hospitals in Riyadh in order to collect more information related to patients with MERS-CoV infections. Copyright © 2016

  15. In vitro and in vivo models of Staphylococcus aureus endophthalmitis implicate specific nutrients in ocular infection.

    Directory of Open Access Journals (Sweden)

    Ama Sadaka

    Full Text Available To define global transcriptional responses of Staphylococcus aureus and its codY mutant (CodY is a transcription regulator of virulence and metabolic genes in response to branched-chain amino acids when growing in bovine aqueous (AH and vitreous humor (VH in vitro, and to investigate the impact of codY deletion on S. aureus virulence in a novel murine anterior chamber (AC infection model.For the in vitro model, differential transcriptomic gene expression of S. aureus and its codY mutant grown in chemically defined medium (CDM, AH, and VH was analyzed. Furthermore, the strains were inoculated into the AC of mice. Changes in bacterial growth, electroretinography and inflammation scores were monitored.Bovine AH and VH provide sufficient nutrition for S. aureus growth in vitro. Transcriptome analysis identified 72 unique open reading frames differentially regulated ≥10-fold between CDM, AH, and VH. In the AC model, we found comparable growth of the codY mutant and wild type strains in vivo. Average inflammation scores and retinal function were significantly worse for codY mutant-infected eyes at 24 h post-infection.Our in vitro bovine AH and VH models identified likely nutrient sources for S. aureus in the ocular milieu. The in vivo model suggests that control of branched-chain amino acid availability has therapeutic potential in limiting S. aureus endophthalmitis severity.

  16. Modeling two strains of disease via aggregate-level infectivity curves.

    Science.gov (United States)

    Romanescu, Razvan; Deardon, Rob

    2016-04-01

    Well formulated models of disease spread, and efficient methods to fit them to observed data, are powerful tools for aiding the surveillance and control of infectious diseases. Our project considers the problem of the simultaneous spread of two related strains of disease in a context where spatial location is the key driver of disease spread. We start our modeling work with the individual level models (ILMs) of disease transmission, and extend these models to accommodate the competing spread of the pathogens in a two-tier hierarchical population (whose levels we refer to as 'farm' and 'animal'). The postulated interference mechanism between the two strains is a period of cross-immunity following infection. We also present a framework for speeding up the computationally intensive process of fitting the ILM to data, typically done using Markov chain Monte Carlo (MCMC) in a Bayesian framework, by turning the inference into a two-stage process. First, we approximate the number of animals infected on a farm over time by infectivity curves. These curves are fit to data sampled from farms, using maximum likelihood estimation, then, conditional on the fitted curves, Bayesian MCMC inference proceeds for the remaining parameters. Finally, we use posterior predictive distributions of salient epidemic summary statistics, in order to assess the model fitted.

  17. High Throughput Screen for Novel Antimicrobials using a Whole Animal Infection Model

    Science.gov (United States)

    Moy, Terence I.; Conery, Annie L.; Larkins-Ford, Jonah; Wu, Gang; Mazitschek, Ralph; Casadei, Gabriele; Lewis, Kim; Carpenter, Anne E.; Ausubel, Frederick M.

    2009-01-01

    The nematode Caenorhabditis elegans is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C. elegans can be infected with a broad range of human pathogens, including Enterococcus faecalis, an important human nosocomial pathogen with a mortality rate of up to 37% that is increasingly acquiring resistance to antibiotics. Here, we describe an automated, high throughput screen of 37,200 compounds and natural product extracts for those that enhance survival of C. elegans infected with E. faecalis. The screen uses a robot to accurately dispense live, infected animals into 384-well plates, and automated microscopy and image analysis to generate quantitative, high content data. We identified 28 compounds and extracts that were not previously reported to have antimicrobial properties, including 6 structural classes that cure infected C. elegans animals but do not affect the growth of the pathogen in vitro, thus acting by a mechanism of action distinct from antibiotics currently in clinical use. Our versatile and robust screening system can be easily adapted for other whole animal assays to probe a broad range of biological processes. PMID:19572548

  18. A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection.

    Science.gov (United States)

    Braian, Clara; Svensson, Mattias; Brighenti, Susanna; Lerm, Maria; Parasa, Venkata R

    2015-10-05

    Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us understand the disease mechanisms and advance the discoveries of new treatment options. In vitro cell cultures of monolayers or co-cultures lack the three-dimensional (3D) environment and tissue responses. Herein, we describe an innovative in vitro model of a human lung tissue, which holds promise to be an effective tool for studying the complex events that occur during infection with Mycobacterium tuberculosis (M. tuberculosis). The 3D tissue model consists of tissue-specific epithelial cells and fibroblasts, which are cultured in a matrix of collagen on top of a porous membrane. Upon air exposure, the epithelial cells stratify and secrete mucus at the apical side. By introducing human primary macrophages infected with M. tuberculosis to the tissue model, we have shown that immune cells migrate into the infected-tissue and form early stages of TB granuloma. These structures recapitulate the distinct feature of human TB, the granuloma, which is fundamentally different or not commonly observed in widely used experimental animal models. This organotypic culture method enables the 3D visualization and robust quantitative analysis that provides pivotal information on spatial and temporal features of host cell-pathogen interactions. Taken together, the lung tissue model provides a physiologically relevant tissue micro-environment for studies on TB. Thus, the lung tissue model has potential implications for both basic mechanistic and applied studies. Importantly, the model allows addition or manipulation of individual cell types, which thereby widens its use for modelling a variety of infectious diseases that affect the lungs.

  19. [Etiological analysis and establishment of a discriminant model for lower respiratory tract infections in hospitalized patients].

    Science.gov (United States)

    Chen, Y S; Lin, X H; Li, H R; Hua, Z D; Lin, M Q; Huang, W S; Yu, T; Lyu, H Y; Mao, W P; Liang, Y Q; Peng, X R; Chen, S J; Zheng, H; Lian, S Q; Hu, X L; Yao, X Q

    2017-12-12

    Objective: To analyze the pathogens of lower respiratory tract infection(LRTI) including bacterial, viral and mixed infection, and to establish a discriminant model based on clinical features in order to predict the pathogens. Methods: A total of 243 hospitalized patients with lower respiratory tract infections were enrolled in Fujian Provincial Hospital from April 2012 to September 2015. The clinical data and airway (sputum and/or bronchoalveolar lavage) samples were collected. Microbes were identified by traditional culture (for bacteria), loop-mediated isothermal amplification(LAMP) and gene sequencing (for bacteria and atypical pathogen), or Real-time quantitative polymerase chain reaction (Real-time PCR)for viruses. Finally, a discriminant model was established by using the discriminant analysis methods to help to predict bacterial, viral and mixed infections. Results: Pathogens were detected in 53.9% (131/243) of the 243 cases.Bacteria accounted for 23.5%(57/243, of which 17 cases with the virus, 1 case with Mycoplasma pneumoniae and virus), mainly Pseudomonas Aeruginosa and Klebsiella Pneumonia. Atypical pathogens for 4.9% (12/243, of which 3 cases with the virus, 1 case of bacteria and viruses), all were mycoplasma pneumonia. Viruses for 34.6% (84/243, of which 17 cases of bacteria, 3 cases with Mycoplasma pneumoniae, 1 case with Mycoplasma pneumoniae and bacteria) of the cases, mainly Influenza A virus and Human Cytomegalovirus, and other virus like adenovirus, human parainfluenza virus, respiratory syncytial virus, human metapneumovirus, human boca virus were also detected fewly. Seven parameters including mental status, using antibiotics prior to admission, complications, abnormal breath sounds, neutrophil alkaline phosphatase (NAP) score, pneumonia severity index (PSI) score and CRUB-65 score were enrolled after univariate analysis, and discriminant analysis was used to establish the discriminant model by applying the identified pathogens as the

  20. Multiple time scales in modeling the incidence of infections acquired in intensive care units

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    Martin Wolkewitz

    2016-09-01

    Full Text Available Abstract Background When patients are admitted to an intensive care unit (ICU their risk of getting an infection will be highly depend on the length of stay at-risk in the ICU. In addition, risk of infection is likely to vary over calendar time as a result of fluctuations in the prevalence of the pathogen on the ward. Hence risk of infection is expected to depend on two time scales (time in ICU and calendar time as well as competing events (discharge or death and their spatial location. The purpose of this paper is to develop and apply appropriate statistical models for the risk of ICU-acquired infection accounting for multiple time scales, competing risks and the spatial clustering of the data. Methods A multi-center data base from a Spanish surveillance network was used to study the occurrence of an infection due to Methicillin-resistant Staphylococcus aureus (MRSA. The analysis included 84,843 patient admissions between January 2006 and December 2011 from 81 ICUs. Stratified Cox models were used to study multiple time scales while accounting for spatial clustering of the data (patients within ICUs and for death or discharge as competing events for MRSA infection. Results Both time scales, time in ICU and calendar time, are highly associated with the MRSA hazard rate and cumulative risk. When using only one basic time scale, the interpretation and magnitude of several patient-individual risk factors differed. Risk factors concerning the severity of illness were more pronounced when using only calendar time. These differences disappeared when using both time scales simultaneously. Conclusions The time-dependent dynamics of infections is complex and should be studied with models allowing for multiple time scales. For patient individual risk-factors we recommend stratified Cox regression models for competing events with ICU time as the basic time scale and calendar time as a covariate. The inclusion of calendar time and stratification by ICU

  1. THE INFLUENCE OF TESTICLE EXTRACT ON THE INTRADERMAL SPREAD OF INJECTED FLUIDS AND PARTICLES.

    Science.gov (United States)

    Hoffman, D C; Duran-Reynals, F

    1931-02-28

    The experiments in this paper show that testicle extract causes India ink particles and those of Prussian blue to spread much more extensively through the intercellular spaces than similar suspensions made with Ringer's solution. Methylene blue inoculated intravenously localizes more extensively in areas previously injected with testicle extracts than in control areas receiving injections of tissue extracts without enhancing power. Kidney extracts have this property to a less degree, whereas spleen extracts and blood serum are devoid of it. The spreading power of extracts is destroyed by heating at 60 degrees C. for 30 minutes, as is also the power to enhance infections. The precise mode of action of the Reynals factor is not known, but the results of the experiments here presented suggest that it may depend at least in part on the property whereby testicle extract increases the spread of injected material and alters the permeability of tissue cells. It is not inconceivable that changes in permeability facilitate the passage of vaccine virus through the endothelial cells of the blood and lymph vessels, and lead to the generalized vaccinia which is of frequent occurrence in the reported results (20). It has been shown that fluids and suspensions of inert particles are spread by the extract.B. tetanus and B. coli exotoxins and trypsin were not enhanced at all in their action despite the fact that they were spread through a more extensive area in the tissues. Viruses, on the other hand, are markedly influenced and in this respect resemble bacteria, not toxins and enzymes. It appears probable that a definite capacity for multiplication on the part of an injected substance is required if its pathogenic effects are to be enhanced. It may be concluded tentatively that the enhancing power of the testicle extract may depend on that property which not only spreads the injected material through a larger area but renders the tissue cells more easily penetrable by the agents.

  2. Dengue virus infection: current concepts in immune mechanisms and lessons from murine models

    Science.gov (United States)

    Guabiraba, Rodrigo; Ryffel, Bernhard

    2014-01-01

    Dengue viruses (DENV), a group of four serologically distinct but related flaviviruses, are responsible for one of the most important emerging viral diseases. This mosquito-borne disease has a great impact in tropical and subtropical areas of the world in terms of illness, mortality and economic costs, mainly due to the lack of approved vaccine or antiviral drugs. Infections with one of the four serotypes of DENV (DENV-1–4) result in symptoms ranging from an acute, self-limiting febrile illness, dengue fever, to severe dengue haemorrhagic fever or dengue shock syndrome. We reviewed the existing mouse models of infection, including the DENV-2-adapted strain P23085. The role of CC chemokines, interleukin-17 (IL-17), IL-22 and invariant natural killer T cells in mediating the exacerbation of disease in immune-competent mice is highlighted. Investigations in both immune-deficient and immune-competent mouse models of DENV infection may help to identify key host–pathogen factors and devise novel therapies to restrain the systemic and local inflammatory responses associated with severe DENV infection. PMID:24182427

  3. Establishment of a bacterial infection model using the European honeybee, Apis mellifera L.

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    Kenichi Ishii

    Full Text Available Injection of human pathogenic bacteria (Pseudomonas aeruginosa, Serratia marcescens, Salmonella enterica, Staphylococcus aureus, and Listeria monocytogenes into the hemocoel of honeybee (Apis mellifera L. workers kills the infected bees. The bee-killing effects of the pathogens were affected by temperature, and the LD₅₀ values at 37°C were more than 100-fold lower than those at 15°C. Gene-disrupted S. aureus mutants of virulence genes such as agrA, saeS, arlR, srtA, hla, and hlb had attenuated bee-killing ability. Nurse bees were less susceptible than foragers and drones to S. aureus infection. Injection of antibiotics clinically used for humans had therapeutic effects against S. aureus infections of bees, and the ED₅₀ values of these antibiotics were comparable with those determined in mammalian models. Moreover, the effectiveness of orally administered antibiotics was consistent between honeybees and mammals. These findings suggest that the honeybee could be a useful model for assessing the pathogenesis of human-infecting bacteria and the effectiveness of antibiotics.

  4. Plasma-treated water eliminates Streptococcus mutans in infected dentin model.

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    Tasaki, Tatsuya; Ohshima, Tomoko; Usui, Emi; Ikawa, Satoshi; Kitano, Katsuhisa; Maeda, Nobuko; Momoi, Yasuko

    2017-07-26

    Non-mechanical procedures for removing caries-infected dentin are warranted in dentistry. We previously demonstrated the marked sterilization effect for direct irradiation of low-temperature plasma using dentin model infected with Streptococcus mutans. However it requires 180 s of intraoral plasma irradiation to eliminate bacteria. We alternatively investigated whether plasma-treated water (PTW), i.e., pure water exposed to plasma in an atmosphere, has a same bactericidal activity with the plasma irradiation. In the infected dentin model, the viable S. mutans counts recovered by bur at depth of 0.8-2.4 mm from the cavity floor were 10 4 -10 6 CFU/round bur. After PTW application for only 10 s, the count was significantly decreased to below the detection limit (2.5 CFU/round bur) or 3.0±5.0 CFU/round bur. Since the bactericidal activity of PTW is rapidly deactivated at body temperature (37°C), PTW is likely to be biocompatible and holds significant potential for non-mechanical procedures for removing caries-infected dentin.

  5. Estimating the true accuracy of diagnostic tests for dengue infection using bayesian latent class models.

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    Wirichada Pan-ngum

    Full Text Available Accuracy of rapid diagnostic tests for dengue infection has been repeatedly estimated by comparing those tests with reference assays. We hypothesized that those estimates might be inaccurate if the accuracy of the reference assays is not perfect. Here, we investigated this using statistical modeling.Data from a cohort study of 549 patients suspected of dengue infection presenting at Colombo North Teaching Hospital, Ragama, Sri Lanka, that described the application of our reference assay (a combination of Dengue IgM antibody capture ELISA and IgG antibody capture ELISA and of three rapid diagnostic tests (Panbio NS1 antigen, IgM antibody and IgG antibody rapid immunochromatographic cassette tests were re-evaluated using bayesian latent class models (LCMs. The estimated sensitivity and specificity of the reference assay were 62.0% and 99.6%, respectively. Prevalence of dengue infection (24.3%, and sensitivities and specificities of the Panbio NS1 (45.9% and 97.9%, IgM (54.5% and 95.5% and IgG (62.1% and 84.5% estimated by bayesian LCMs were significantly different from those estimated by assuming that the reference assay was perfect. Sensitivity, specificity, PPV and NPV for a combination of NS1, IgM and IgG cassette tests on admission samples were 87.0%, 82.8%, 62.0% and 95.2%, respectively.Our reference assay is an imperfect gold standard. In our setting, the combination of NS1, IgM and IgG rapid diagnostic tests could be used on admission to rule out dengue infection with a high level of accuracy (NPV 95.2%. Further evaluation of rapid diagnostic tests for dengue infection should include the use of appropriate statistical models.

  6. Comparative In Vivo Efficacies of Tedizolid in Neutropenic versus Immunocompetent Murine Streptococcus pneumoniae Lung Infection Models.

    Science.gov (United States)

    Abdelraouf, Kamilia; Nicolau, David P

    2017-01-01

    Given that tedizolid exhibits substantial lung penetration, we hypothesize that it could achieve good efficacy against Streptococcus pneumoniae lung infections. We evaluated the pharmacodynamics of tedizolid for treatment of S. pneumoniae lung infections and compared the efficacies of tedizolid human-simulated epithelial lining fluid (ELF) exposures in immunocompetent and neutropenic murine lung infection models. ICR mice were rendered neutropenic via intraperitoneal cyclophosphamide injections and then inoculated intranasally with S. pneumoniae suspensions. Immunocompetent CBA/J mice were inoculated similarly. Single daily tedizolid doses were administered 4 h postinoculation (termed 0 h). Changes in log 10 CFU at 24 h compared with 0-h controls were estimated. Ratios of area under the free-drug concentration-time curve to MIC (fAUC 0-24 /MIC) required to achieve various efficacy endpoints against each isolate were estimated using the Hill equation. Tedizolid doses in neutropenic and immunocompetent mice that mimic the human-simulated ELF exposure were examined. Stasis, 1-log reduction, and 2-log reduction were achieved at fAUC 0-24 /MIC of 8.96, 24.62, and 48.34, respectively, in immunocompetent mice and 19.21, 48.29, and 103.95, respectively, in neutropenic mice. Tedizolid at 40 mg/kg of body weight/day and 55 mg/kg/day in immunocompetent and neutropenic mice, respectively, resulted in ELF AUC 0-24 comparable to that achieved in humans following a 200-mg once-daily clinical dose. These human-simulated ELF exposures were adequate to attain >2-log reduction in bacterial burden at 24 h in 3 out of 4 isolates in both models and 1.58- and 0.74-log reductions with the fourth isolate in immunocompetent and neutropenic mice, respectively. Tedizolid showed potent in vivo efficacy against S. pneumoniae in both immunocompetent and neutropenic lung infection models, which support its consideration for S. pneumoniae lung infections. Copyright © 2016 American Society for

  7. Strengths and Limitations of Model Systems for the Study of Urinary Tract Infections and Related Pathologies

    Science.gov (United States)

    Barber, Amelia E.; Norton, J. Paul; Wiles, Travis J.

    2016-01-01

    SUMMARY Urinary tract infections (UTIs) are some of the most common bacterial infections worldwide and are a source of substantial morbidity among otherwise healthy women. UTIs can be caused by a variety of microbes, but the predominant etiologic agent of these infections is uropathogenic Escherichia coli (UPEC). An especially troubling feature of UPEC-associated UTIs is their high rate of recurrence. This problem is compounded by the drastic increase in the global incidence of antibiotic-resistant UPEC strains over the past 15 years. The need for more-effective treatments for UTIs is driving research aimed at bettering our understanding of the virulence mechanisms and host-pathogen interactions that occur during the course of these infections. Surrogate models of human infection, including cell culture systems and the use of murine, porcine, avian, teleost (zebrafish), and nematode hosts, are being employed to define host and bacterial factors that modulate the pathogenesis of UTIs. These model systems are revealing how UPEC strains can avoid or overcome host defenses and acquire scarce nutrients while also providing insight into the virulence mechanisms used by UPEC within compromised individuals, such as catheterized patients. Here, we summarize our current understanding of UTI pathogenesis while also giving an overview of the model systems used to study the initiation, persistence, and recurrence of UTIs and life-threatening sequelae like urosepsis. Although we focus on UPEC, the experimental systems described here can also provide valuable insight into the disease processes associated with other bacterial pathogens both within the urinary tract and elsewhere within the host. PMID:26935136

  8. Plasmablast Response to Primary Rhesus Cytomegalovirus (CMV) Infection in a Monkey Model of Congenital CMV Transmission.

    Science.gov (United States)

    Fan, Qihua; Nelson, Cody S; Bialas, Kristy M; Chiuppesi, Flavia; Amos, Joshua; Gurley, Thaddeus C; Marshall, Dawn Jones; Eudailey, Joshua; Heimsath, Holly; Himes, Jonathon; Deshpande, Ashlesha; Walter, Mark R; Wussow, Felix; Diamond, Don J; Barry, Peter A; Moody, M Anthony; Kaur, Amitinder; Permar, Sallie R

    2017-05-01

    Human cytomegalovirus (HCMV) is the most common congenital infection worldwide and the leading infectious cause of neurologic deficits and hearing loss in newborns. Development of a maternal HCMV vaccine to prevent vertical virus transmission is a high priority, yet protective maternal immune responses following acute infection are poorly understood. To characterize the maternal humoral immune response to primary CMV infection, we investigated the plasmablast and early antibody repertoire using a nonhuman primate model with two acutely rhesus CMV (RhCMV)-infected animals-a CD4 + T cell-depleted dam that experienced fetal loss shortly after vertical RhCMV transmission and an immunocompetent dam that did not transmit RhCMV to her infant. Compared to the CD4 + T cell-depleted dam that experienced fetal loss, the immunocompetent, nontransmitting dam had a more rapid and robust plasmablast response that produced a high proportion of RhCMV-reactive antibodies, including the first identified monoclonal antibody specific for soluble and membrane-associated RhCMV envelope glycoprotein B (gB). Additionally, we noted that plasmablast RhCMV-specific antibodies had variable gene usage and maturation similar to those observed in a monkey chronically coinfected with simian immunodeficiency virus (SIV) and RhCMV. This study reveals characteristics of the early maternal RhCMV-specific humoral immune responses to primary RhCMV infection in rhesus monkeys and may contribute to a future understanding of what antibody responses should be targeted by a vaccine to eliminate congenital HCMV transmission. Furthermore, the identification of an RhCMV gB-specific monoclonal antibody underscores the possibility of modeling future HCMV vaccine strategies in this nonhuman primate model. Copyright © 2017 American Society for Microbiology.

  9. Defining New Therapeutics Using a More Immunocompetent Mouse Model of Antibody-Enhanced Dengue Virus Infection

    Science.gov (United States)

    Pinto, Amelia K.; Brien, James D.; Lam, Chia-Ying Kao; Johnson, Syd; Chiang, Cindy; Hiscott, John; Sarathy, Vanessa V.; Barrett, Alan D.; Shresta, Sujan

    2015-01-01

    ABSTRACT With over 3.5 billion people at risk and approximately 390 million human infections per year, dengue virus (DENV) disease strains health care resources worldwide. Previously, we and others established models for DENV pathogenesis in mice that completely lack subunits of the receptors (Ifnar and Ifngr) for type I and type II interferon (IFN) signaling; however, the utility of these models is limited by the pleotropic effect of these cytokines on innate and adaptive immune system development and function. Here, we demonstrate that the specific deletion of Ifnar expression on subsets of murine myeloid cells (LysM Cre+ Ifnarflox/flox [denoted as Ifnarf/f herein]) resulted in enhanced DENV replication in vivo. The administration of subneutralizing amounts of cross-reactive anti-DENV monoclonal antibodies to LysM Cre+ Ifnarf/f mice prior to infection with DENV serotype 2 or 3 resulted in antibody-dependent enhancement (ADE) of infection with many of the characteristics associated with severe DENV disease in humans, including plasma leakage, hypercytokinemia, liver injury, hemoconcentration, and thrombocytopenia. Notably, the pathogenesis of severe DENV-2 or DENV-3 infection in LysM Cre+ Ifnarf/f mice was blocked by pre- or postexposure administration of a bispecific dual-affinity retargeting molecule (DART) or an optimized RIG-I receptor agonist that stimulates innate immune responses. Our findings establish a more immunocompetent animal model of ADE of infection with multiple DENV serotypes in which disease is inhibited by treatment with broad-spectrum antibody derivatives or innate immune stimulatory agents. PMID:26374123

  10. A Delayed Virus Infection Model with Cell-to-Cell Transmission and CTL Immune Response

    Science.gov (United States)

    Yang, Yu; Zhang, Tonghua; Xu, Yancong; Zhou, Jinling

    In this paper, a delayed virus infection model with cell-to-cell transmission and CTL immune response is investigated. In the model, time delay is incorporated into the CTL response. By constructing Lyapunov functionals, global dynamical properties of the two boundary equilibria are established. Our results show that time delay in the CTL response process may lead to sustained oscillation. To further investigate the nature of the oscillation, we apply the method of multiple time scales to calculate the normal form on the center manifold of the model. At the end of the paper, numerical simulations are carried out, which support our theoretical results.

  11. Aotus infulatus monkey is susceptible to Plasmodium falciparum infection and may constitute an alternative experimental model for malaria

    Directory of Open Access Journals (Sweden)

    Carvalho Leonardo JM

    2000-01-01

    Full Text Available Aotus is one of the WHO-recommended primate models for studies in malaria, and several species can be infected with Plasmodium falciparum or P. vivax. Here we describe the successful infection of the species A. infulatus from eastern Amazon with blood stages of P. falciparum. Both intact and splenectomized animals were susceptible to infection; the intact ones were able to keep parasitemias at lower levels for several days, but developed complications such as severe anemia; splenectomized monkeys developed higher parasitemias but no major complications. We conclude that A. infulatus is susceptible to P. falciparum infection and may represent an alternative model for studies in malaria.

  12. A controlled human malaria infection model enabling evaluation of transmission-blocking interventions.

    Science.gov (United States)

    Collins, Katharine A; Wang, Claire Yt; Adams, Matthew; Mitchell, Hayley; Rampton, Melanie; Elliott, Suzanne; Reuling, Isaie J; Bousema, Teun; Sauerwein, Robert; Chalon, Stephan; Möhrle, Jörg J; McCarthy, James S

    2018-03-12

    Drugs and vaccines that can interrupt the transmission of Plasmodium falciparum will be important for malaria control and elimination. However, models for early clinical evaluation of candidate transmission-blocking interventions are currently unavailable. Here, we describe a new model for evaluating malaria transmission from humans to Anopheles mosquitoes using controlled human malaria infection (CHMI). Seventeen healthy malaria-naive volunteers underwent CHMI by intravenous inoculation of P. falciparum-infected erythrocytes to initiate blood-stage infection. Seven to eight days after inoculation, participants received piperaquine (480 mg) to attenuate asexual parasite replication while allowing gametocytes to develop and mature. Primary end points were development of gametocytemia, the transmissibility of gametocytes from humans to mosquitoes, and the safety and tolerability of the CHMI transmission model. To investigate in vivo gametocytocidal drug activity in this model, participants were either given an experimental antimalarial, artefenomel (500 mg), or a known gametocytocidal drug, primaquine (15 mg), or remained untreated during the period of gametocyte carriage. Male and female gametocytes were detected in all participants, and transmission to mosquitoes was achieved from 8 of 11 (73%) participants evaluated. Compared with results in untreated controls (n = 7), primaquine (15 mg, n = 5) significantly reduced gametocyte burden (P = 0.01), while artefenomel (500 mg, n = 4) had no effect. Adverse events (AEs) were mostly mild or moderate. Three AEs were assessed as severe - fatigue, elevated alanine aminotransferase, and elevated aspartate aminotransferase - and were attributed to malaria infection. Transaminase elevations were transient, asymptomatic, and resolved without intervention. We report the safe and reproducible induction of P. falciparum gametocytes in healthy malaria-naive volunteers at densities infectious to mosquitoes, thereby demonstrating the

  13. Validation of a Novel Murine Wound Model of Acinetobacter baumannii Infection

    Science.gov (United States)

    Thompson, Mitchell G.; Black, Chad C.; Pavlicek, Rebecca L.; Honnold, Cary L.; Wise, Matthew C.; Alamneh, Yonas A.; Moon, Jay K.; Kessler, Jennifer L.; Si, Yuanzheng; Williams, Robert; Yildirim, Suleyman; Kirkup, Benjamin C.; Green, Romanza K.; Hall, Eric R.; Palys, Thomas J.

    2014-01-01

    Patients recovering from traumatic injuries or surgery often require weeks to months of hospitalization, increasing the risk for wound and surgical site infections caused by ESKAPE pathogens, which include A. baumannii (the ESKAPE pathogens are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). As new therapies are being developed to counter A. baumannii infections, animal models are also needed to evaluate potential treatments. Here, we present an excisional, murine wound model in which a diminutive inoculum of a clinically relevant, multidrug-resistant A. baumannii isolate can proliferate, form biofilms, and be effectively treated with antibiotics. The model requires a temporary, cyclophosphamide-induced neutropenia to establish an infection that can persist. A 6-mm-diameter, full-thickness wound was created in the skin overlying the thoracic spine, and after the wound bed was inoculated, it was covered with a dressing for 7 days. Uninoculated control wounds healed within 13 days, whereas infected, placebo-treated wounds remained unclosed beyond 21 days. Treated and untreated wounds were assessed with multiple quantitative and qualitative techniques that included gross pathology, weight loss and recovery, wound closure, bacterial burden, 16S rRNA community profiling, histopathology, peptide nucleic acid-fluorescence in situ hybridization, and scanning electron microscopy assessment of biofilms. The range of differences that we are able to identify with these measures in antibiotic- versus placebo-treated animals provides a clear window within which novel antimicrobial therapies can be assessed. The model can be used to evaluate antimicrobials for their ability to reduce specific pathogen loads in wounded tissues and clear biofilms. Ultimately, the mouse model approach allows for highly powered studies and serves as an initial multifaceted in vivo assessment prior to

  14. Geostatistical modelling of soil-transmitted helminth infection in Cambodia: do socioeconomic factors improve predictions?

    Science.gov (United States)

    Karagiannis-Voules, Dimitrios-Alexios; Odermatt, Peter; Biedermann, Patricia; Khieu, Virak; Schär, Fabian; Muth, Sinuon; Utzinger, Jürg; Vounatsou, Penelope

    2015-01-01

    Soil-transmitted helminth infections are intimately connected with poverty. Yet, there is a paucity of using socioeconomic proxies in spatially explicit risk profiling. We compiled household-level socioeconomic data pertaining to sanitation, drinking-water, education and nutrition from readily available Demographic and Health Surveys, Multiple Indicator Cluster Surveys and World Health Surveys for Cambodia and aggregated the data at village level. We conducted a systematic review to identify parasitological surveys and made every effort possible to extract, georeference and upload the data in the open source Global Neglected Tropical Diseases database. Bayesian geostatistical models were employed to spatially align the village-aggregated socioeconomic predictors with the soil-transmitted helminth infection data. The risk of soil-transmitted helminth infection was predicted at a grid of 1×1km covering Cambodia. Additionally, two separate individual-level spatial analyses were carried out, for Takeo and Preah Vihear provinces, to assess and quantify the association between soil-transmitted helminth infection and socioeconomic indicators at an individual level. Overall, we obtained socioeconomic proxies from 1624 locations across the country. Surveys focussing on soil-transmitted helminth infections were extracted from 16 sources reporting data from 238 unique locations. We found that the risk of soil-transmitted helminth infection from 2000 onwards was considerably lower than in surveys conducted earlier. Population-adjusted prevalences for school-aged children from 2000 onwards were 28.7% for hookworm, 1.5% for Ascaris lumbricoides and 0.9% for Trichuris trichiura. Surprisingly, at the country-wide analyses, we did not find any significant association between soil-transmitted helminth infection and village-aggregated socioeconomic proxies. Based also on the individual-level analyses we conclude that socioeconomic proxies might not be good predictors at an

  15. A hepatitis C virus infection model with time-varying drug effectiveness: solution and analysis.

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    Jessica M Conway

    2014-08-01

    Full Text Available Simple models of therapy for viral diseases such as hepatitis C virus (HCV or human immunodeficiency virus assume that, once therapy is started, the drug has a constant effectiveness. More realistic models have assumed either that the drug effectiveness depends on the drug concentration or that the effectiveness varies over time. Here a previously introduced varying-effectiveness (VE model is studied mathematically in the context of HCV infection. We show that while the model is linear, it has no closed-form solution due to the time-varying nature of the effectiveness. We then show that the model can be transformed into a Bessel equation and derive an analytic solution in terms of modified Bessel functions, which are defined as infinite series, with time-varying arguments. Fitting the solution to data from HCV infected patients under therapy has yielded values for the parameters in the model. We show that for biologically realistic parameters, the predicted viral decay on therapy is generally biphasic and resembles that predicted by constant-effectiveness (CE models. We introduce a general method for determining the time at which the transition between decay phases occurs based on calculating the point of maximum curvature of the viral decay curve. For the parameter regimes of interest, we also find approximate solutions for the VE model and establish the asymptotic behavior of the system. We show that the rate of second phase decay is determined by the death rate of infected cells multiplied by the maximum effectiveness of therapy, whereas the rate of first phase decline depends on multiple parameters including the rate of increase of drug effectiveness with time.

  16. External Validation of Prediction Models for Pneumonia in Primary Care Patients with Lower Respiratory Tract Infection

    DEFF Research Database (Denmark)

    Schierenberg, Alwin; Minnaard, Margaretha C; Hopstaken, Rogier M

    2016-01-01

    BACKGROUND: Pneumonia remains difficult to diagnose in primary care. Prediction models based on signs and symptoms (S&S) serve to minimize the diagnostic uncertainty. External validation of these models is essential before implementation into routine practice. In this study all published S&S models...... for prediction of pneumonia in primary care were externally validated in the individual patient data (IPD) of previously performed diagnostic studies. METHODS AND FINDINGS: S&S models for diagnosing pneumonia in adults presenting to primary care with lower respiratory tract infection and IPD for validation were...... identified through a systematical search. Six prediction models and IPD of eight diagnostic studies (N total = 5308, prevalence pneumonia 12%) were included. Models were assessed on discrimination and calibration. Discrimination was measured using the pooled Area Under the Curve (AUC) and delta AUC...

  17. Epidemic model of HIV infection and AIDS in Argentina. Status in 1990 and predictive estimates.

    Science.gov (United States)

    Raggi, R; Blanco, G A

    1992-01-01

    The purpose of this paper was to evaluate the prevalence of HIV infection and AIDS in Argentina, to study the dynamics of the spread of HIV and to predict the future course by means of an epidemic model. The model was constructed using differential equations to describe the interactions between members of the various groups at risk. The functional form of the solutions was used in a back calculation procedure using data from cohort studies which were done in other countries (U.S.A. and France) together with data of AIDS cases reported to the National AIDS Program, to determine the time evolution of HIV-infection in each of the groups at risk defined. Results show that HIV was introduced in Argentina during the early 80's and affected persons of the homosexual/bisexual group in a first stage. In April 1990 it was estimated that there were a total of 34,131 HIV-infected persons. Intravenous drug users (IVDU) represented 39.5%, homosexual/bisexual men 47.6% and heterosexual adults 11%. It is estimated that in December 1992 there will be 107,946 HIV-infected persons where heterosexuals contribute with more than 20% of that value. AIDS cases predicted for the same period are 4130, with 1958 among homosexual/bisexual, 1483 among IVDU, 449 in heterosexual adults, 153 in children under 4 years old and 87 among hemophiliacs or patients with blood coagulation disorders. By the end of 1994 the model predicts more than 200,000 HIV infected persons with an important proportion of heterosexual adults and more than 12,000 AIDS cases. The values of this period must be considered as a future possible scenario if the present spread conditions are preserved. Infection among heterosexual adults is at the present time in a first and exponential phase of spread and dominated by transmission from IVDU group and bisexual men. It is concluded that the future course of AIDS epidemic in Argentina may be particularly influenced by changes in the heterosexual behavior particularly in those

  18. A lethal disease model for hantavirus pulmonary syndrome in immunosuppressed Syrian hamsters infected with Sin Nombre virus.

    Science.gov (United States)

    Brocato, Rebecca L; Hammerbeck, Christopher D; Bell, Todd M; Wells, Jay B; Queen, Laurie A; Hooper, Jay W

    2014-01-01

    Sin Nombre virus (SNV) is a rodent-borne hantavirus that causes hantavirus pulmonary syndrome (HPS) predominantly in North America. SNV infection of immunocompetent hamsters results in an asymptomatic infection; the only lethal disease model for a pathogenic hantavirus is Andes virus (ANDV) infection of Syrian hamsters. Efforts to create a lethal SNV disease model in hamsters by repeatedly passaging virus through the hamster have demonstrated increased dissemination of the virus but no signs of disease. In this study, we demonstrate that immunosuppression of hamsters through the administration of a combination of dexamethasone and cyclophosphamide, followed by infection with SNV, results in a vascular leak syndrome that accurately mimics both HPS disease in humans and ANDV infection of hamsters. Immunosuppressed hamsters infected with SNV have a mean number of days to death of 13 and display clinical signs associated with HPS, including pulmonary edema. Viral antigen was widely detectable throughout the pulmonary endothelium. Histologic analysis of lung sections showed marked inflammation and edema within the alveolar septa of SNV-infected hamsters, results which are similar to what is exhibited by hamsters infected with ANDV. Importantly, SNV-specific neutralizing polyclonal antibody administered 5 days after SNV infection conferred significant protection against disease. This experiment not only demonstrated that the disease was caused by SNV, it also demonstrated the utility of this animal model for testing candidate medical countermeasures. This is the first report of lethal disease caused by SNV in an adult small-animal model.

  19. Dynamics of an HIV-1 infection model with cell mediated immunity

    Science.gov (United States)

    Yu, Pei; Huang, Jianing; Jiang, Jiao

    2014-10-01

    In this paper, we study the dynamics of an improved mathematical model on HIV-1 virus with cell mediated immunity. This new 5-dimensional model is based on the combination of a basic 3-dimensional HIV-1 model and a 4-dimensional immunity response model, which more realistically describes dynamics between the uninfected cells, infected cells, virus, the CTL response cells and CTL effector cells. Our 5-dimensional model may be reduced to the 4-dimensional model by applying a quasi-steady state assumption on the variable of virus. However, it is shown in this paper that virus is necessary to be involved in the modeling, and that a quasi-steady state assumption should be applied carefully, which may miss some important dynamical behavior of the system. Detailed bifurcation analysis is given to show that the system has three equilibrium solutions, namely the infection-free equilibrium, the infectious equilibrium without CTL, and the infectious equilibrium with CTL, and a series of bifurcations including two transcritical bifurcations and one or two possible Hopf bifurcations occur from these three equilibria as the basic reproduction number is varied. The mathematical methods applied in this paper include characteristic equations, Routh-Hurwitz condition, fluctuation lemma, Lyapunov function and computation of normal forms. Numerical simulation is also presented to demonstrate the applicability of the theoretical predictions.

  20. Animal models for the study of hepatitis C virus infection and replication.

    Science.gov (United States)

    MacArthur, Kristin L; Wu, Catherine H; Wu, George Y

    2012-06-21

    Hepatitis C virus (HCV) hepatitis, initially termed non-A, non-B hepatitis, has become one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide. With the help of animal models, our understanding of the virus has grown substantially from the time of initial discovery. There is a paucity of available animal models for the study of HCV, mainly because of the selective susceptibility limited to humans and primates. Recent work has focused modification of animals to permit HCV entry, replication and transmission. In this review, we highlight the currently available models for the study of HCV including chimpanzees, tupaia, mouse and rat models. Discussion will include methods of model design as well as the advantages and disadvantages of each model. Particular focus is dedicated to knowledge of pathophysiologic mechanisms of HCV infection that have been elucidated through animal studies. Research within animal models is critically important to establish a complete understanding of HCV infection, which will ultimately form the basis for future treatments and prevention of disease.

  1. Identification of infection- and defense-related genes via a dynamic host-pathogen interaction network using a Candida albicans-zebrafish infection model.

    Science.gov (United States)

    Kuo, Zong-Yu; Chuang, Yung-Jen; Chao, Chun-Cheih; Liu, Fu-Chen; Lan, Chung-Yu; Chen, Bor-Sen

    2013-01-01

    Candida albicans infections and candidiasis are difficult to treat and create very serious therapeutic challenges. In this study, based on interactive time profile microarray data of C. albicans and zebrafish during infection, the infection-related protein-protein interaction (PPI) networks of the two species and the intercellular PPI network between host and pathogen were simultaneously constructed by a dynamic interaction model, modeled as an integrated network consisting of intercellular invasion and cellular defense processes during infection. The signal transduction pathways in regulating morphogenesis and hyphal growth of C. albicans were further investigated based on significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins from which we can gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. The hyphal growth PPI network, zebrafish PPI network and host-pathogen intercellular PPI network were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host, and may help improve medical therapies and facilitate the development of new antifungal drugs. Copyright © 2013 S. Karger AG, Basel.

  2. Waddlia chondrophila induces systemic infection, organ pathology and elicits Th1-associated humoral immunity in a murine model of genital infection

    Directory of Open Access Journals (Sweden)

    Sam eVasilevsky

    2015-11-01

    Full Text Available Waddlia chondrophila is a known bovine abortigenic Chlamydia-related bacterium that has been associated with adverse pregnancy outcomes in human. However, there is a lack of knowledge regarding how W. chondrophila infection spreads, its ability to elicit an immune response and induce pathology. A murine model of genital infection was developed to investigate the pathogenicity and immune response associated with a W. chondrophila infection. Genital inoculation of the bacterial agent resulted in a dose-dependent infection that spread to lumbar lymph nodes and successively to spleen and liver. Bacterial-induced pathology peaked on day 14, characterized by leukocyte infiltration (uterine horn, liver and spleen, necrosis (liver and extramedullary hematopoiesis (spleen. Immunohistochemistry demonstrated the presence of a large number of W. chondrophila in the spleen on day 14. Robust IgG titers were detected by day 14 and remained high until day 52. IgG isotypes consisted of high IgG2a, moderate IgG3 and no detectable IgG1, indicating a Th1-associated immune response. This study provides the first evidence that W. chondrophila genital infection is capable of inducing a systemic infection that spreads to major organs, induces uterus, spleen and liver pathology and elicits a Th1-skewed humoral response. This new animal model will help our understanding of the mechanisms related to intracellular bacteria-induced miscarriages, the most frequent complication of pregnancy that affects one in four women.

  3. Waddlia chondrophila induces systemic infection, organ pathology, and elicits Th1-associated humoral immunity in a murine model of genital infection.

    Science.gov (United States)

    Vasilevsky, Sam; Gyger, Joel; Piersigilli, Alessandra; Pilloux, Ludovic; Greub, Gilbert; Stojanov, Milos; Baud, David

    2015-01-01

    Waddlia chondrophila is a known bovine abortigenic Chlamydia-related bacterium that has been associated with adverse pregnancy outcomes in human. However, there is a lack of knowledge regarding how W. chondrophila infection spreads, its ability to elicit an immune response and induce pathology. A murine model of genital infection was developed to investigate the pathogenicity and immune response associated with a W. chondrophila infection. Genital inoculation of the bacterial agent resulted in a dose-dependent infection that spread to lumbar lymph nodes and successively to spleen and liver. Bacterial-induced pathology peaked on day 14, characterized by leukocyte infiltration (uterine horn, liver, and spleen), necrosis (liver) and extramedullary hematopoiesis (spleen). Immunohistochemistry demonstrated the presence of a large number of W. chondrophila in the spleen on day 14. Robust IgG titers were detected by day 14 and remained high until day 52. IgG isotypes consisted of high IgG2a, moderate IgG3 and no detectable IgG1, indicating a Th1-associated immune response. This study provides the first evidence that W. chondrophila genital infection is capable of inducing a systemic infection that spreads to major organs, induces uterus, spleen, and liver pathology and elicits a Th1-skewed humoral response. This new animal model will help our understanding of the mechanisms related to intracellular bacteria-induced miscarriages, the most frequent complication of pregnancy that affects one in four women.

  4. Anti-Mycobacterium activity of microbial peptides in a silkworm infection model with Mycobacterium smegmatis.

    Science.gov (United States)

    Yagi, Akiho; Uchida, Ryuji; Hamamoto, Hiroshi; Sekimizu, Kazuhisa; Kimura, Ken-Ichi; Tomoda, Hiroshi

    2017-05-01

    An in vivo-mimic silkworm infection model with Mycobacterium smegmatis was established. When silkworms were raised at 37 °C following an injection of M. smegmatis cells (1.25 × 10 7 CFU larva -1  g -1 ) into the silkworm hemolymph, they died within 48 h. Under these conditions, four microbial peptides with anti-M. smegmatis activity, lariatin A, calpinactam, lysocin E and propeptin, exerted therapeutic effects in a dose-dependent manner, and these are also clinically used agents that are active against Mycobacterium tuberculosis. These results indicate that the silkworm infection model with M. smegmatis is practically useful for the screening of therapeutically effective anti-M. tuberculosis antibiotics.

  5. An accurate two-phase approximate solution to the acute viral infection model

    Energy Technology Data Exchange (ETDEWEB)

    Perelson, Alan S [Los Alamos National Laboratory

    2009-01-01

    During an acute viral infection, virus levels rise, reach a peak and then decline. Data and numerical solutions suggest the growth and decay phases are linear on a log scale. While viral dynamic models are typically nonlinear with analytical solutions difficult to obtain, the exponential nature of the solutions suggests approximations can be found. We derive a two-phase approximate solution to the target cell limited influenza model and illustrate the accuracy using data and previously established parameter values of six patients infected with influenza A. For one patient, the subsequent fall in virus concentration was not consistent with our predictions during the decay phase and an alternate approximation is derived. We find expressions for the rate and length of initial viral growth in terms of the parameters, the extent each parameter is involved in viral peaks, and the single parameter responsible for virus decay. We discuss applications of this analysis in antiviral treatments and investigating host and virus heterogeneities.

  6. Transmission of a heterologous clade C Symbiodinium in a model anemone infection system via asexual reproduction

    Directory of Open Access Journals (Sweden)

    Wan-Nan U. Chen

    2016-08-01

    Full Text Available Anemones of genus Exaiptasia are used as model organisms for the study of cnidarian-dinoflagellate (genus Symbiodinium endosymbiosis. However, while most reef-building corals harbor Symbiodinium of clade C, Exaiptasia spp. anemones mainly harbor clade B Symbiodinium (ITS2 type B1 populations. In this study, we reveal for the first time that bleached Exaiptasia pallida anemones can establish a symbiotic relationship with a clade C Symbiodinium (ITS2 type C1. We further found that anemones can transmit the exogenously supplied clade C Symbiodinium cells to their offspring by asexual reproduction (pedal laceration. In order to corroborate the establishment of stable symbiosis, we used microscopic techniques and genetic analyses to examine several generations of anemones, and the results of these endeavors confirmed the sustainability of the system. These findings provide a framework for understanding the differences in infection dynamics between homologous and heterologous dinoflagellate types using a model anemone infection system.

  7. A cocktail of three virulent bacteriophages prevents Vibrio cholerae infection in animal models.

    Science.gov (United States)

    Yen, Minmin; Cairns, Lynne S; Camilli, Andrew

    2017-02-01

    Effective prevention strategies will be essential in reducing disease burden due to bacterial infections. Here we harness the specificity and rapid-acting properties of bacteriophages as a potential prophylaxis therapy for cholera, a severely dehydrating disease caused by Vibrio cholerae. To this end, we test a cocktail of three virulent phages in two animal models of cholera pathogenesis (infant mouse and rabbit models). Oral administration of the phages up to 24 h before V. cholerae challenge reduces colonization of the intestinal tract and prevents cholera-like diarrhea. None of the surviving V. cholerae colonies are resistant to all three phages. Genome sequencing and variant analysis of the surviving colonies indicate that resistance to the phages is largely conferred by mutations in genes required for the production of the phage receptors. For acute infections, such as cholera, phage prophylaxis could provide a strategy to limit the impact of bacterial disease on human health.

  8. Spatially explicit Schistosoma infection risk in eastern Africa using Bayesian geostatistical modelling

    DEFF Research Database (Denmark)

    Schur, Nadine; Hürlimann, Eveline; Stensgaard, Anna-Sofie

    2013-01-01

    surveys on different age-groups and to acquire separate estimates for individuals aged ≤20 years and entire communities. Prevalence estimates were combined with population statistics to obtain country-specific numbers of Schistosoma infections. We estimate that 122 million individuals in eastern Africa...... Africa. Bayesian geostatistical models based on climatic and other environmental data were used to account for potential spatial clustering in spatially structured exposures. Geostatistical variable selection was employed to reduce the set of covariates. Alignment factors were implemented to combine...... are currently infected with either S. mansoni, or S. haematobium, or both species concurrently. Country-specific population-adjusted prevalence estimates range between 12.9% (Uganda) and 34.5% (Mozambique) for S. mansoni and between 11.9% (Djibouti) and 40.9% (Mozambique) for S. haematobium. Our models revealed...

  9. A Single-blind, Split-face, Randomized, Pilot Study Comparing the Effects of Intradermal and Intramuscular Injection of Two Commercially Available Botulinum Toxin A Formulas to Reduce Signs of Facial Aging

    Science.gov (United States)

    Sapra, Priya; Sapra, Sheetal; Khanna, Julie; Mraud, Kelli; Bonadonna, Jennifer

    2017-01-01

    Objective: To examine the effectiveness of intradermal botulinum toxin type A injection in improving skin texture and midface lift while reducing pore size and sebum production, as well as investigate the differences in effectiveness between onabotulinumtoxinA and abobotulinumtoxinA using intradermal and intramuscular injection methods. Design: A 16-week, single-blind, split-face, randomized study. Each patient served as their own control, receiving onabotulinumtoxinA and abobotulinumtoxinA randomized to either the left or right side of the face. Patients received intradermal botulinum toxin type A injections at Week 0 and intramuscular botulinum toxin type A injections at Week 2. Participants: Ten women aged 35 to 65 years who exhibited static rhytids in the glabellar and periorbital area. Measurements: The primary endpoint was efficacy of split-face treatment of intradermal and intramuscular onabotulinumtoxinA and abobotulinumtoxinA as assessed by a blinded evaluator using baseline and post-treatment photographs. The secondary endpoints included safety as assessed by adverse events and patient satisfaction measured by questionnaires completed at baseline and post-treatment. Results: Intradermal injection of botulinum toxin type A led to a statistically significant improvement in skin texture (p=0.004) while also resulting in mild midface lift (p=0.024), but did not provide a significant reduction of pore size and sebum production. There was no statistically significant difference between onabotulinumtoxinA and abobotulinumtoxinA when injected intradermally or intramuscularly. Conclusion: Intradermal injection of botulinum toxin type A appears to be a safe and effective therapy that provides an improvement in facial skin texture and midface lift. Registry: clinicaltrials.gov (ID#: NCT02907268). PMID:28367260

  10. Methodological Study to Develop Standard Operational Protocol on Intramuscular (IM, Intradermal (ID and Subcutaneous Drug Administration for Children

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Bijarania

    2017-10-01

    Full Text Available Introduction: Medicine administration is a major role played by registered nurses. Medicines are prescribed by the physician and dispensed by the pharmacist but responsibility for meticulous administration rests with the registered nurse. It becomes even more important when drugs are to be administered to children. Drug administration via Intramuscular (IM, Intradermal (ID and Subcutaneous route is a complex process. Errors are associated with medicine administration. Aim: The objective of this study was to develop Standard Operational Protocol (SOP for IM, ID and Subcutaneous drug administration and checklist to assess the implementation of the developed SOP. Materials and Methods: A methodological research design adapted to carry out the present study to develop standard operational protocol for IM, ID and subcutaneous drug administration for children, admitted in Advanced Paediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. The study included 58 bedside nurses and 90 observations of medicine administration procedure. Results: The Content Validity Index (CVI was prepared to assess the validity of content (items of SOPs and checklists. Over all Cronbach's-alpha values was calculated to assess the internal consistency of Items in SOPs and checklists. CVI of SOP and checklists were 98.51%, 97.83% and 99.03%. Over all Cronbach'salpha values were calculated 0.96, 0.82 and 0.95. All the nurses felt that SOPs are useful. Conclusion: Valid and feasible SOPs for drug administration in children along with valid and reliable checklists were developed. It is recommended to use this document for drug administration in children to prevent any possible error during drug administration to children.

  11. Antibodies against beta-lactamase can improve ceftazidime treatment of lung infection with beta-lactam-resistant Pseudomonas aeruginosa in a rat model of chronic lung infection

    DEFF Research Database (Denmark)

    Ciofu, Oana; Bagge, Niels; Høiby, Niels

    2002-01-01

    To test the hypothesis that antibodies against the chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) might act as beta-lactamase inhibitors in patients with cystic fibrosis and chronic lung infection with P. aeruginosa, we compared in a rat model of chronic lung infection...... the efficacy of treatment with ceftazidime in beta-lactamase-immunized (group I) and non-immunized (group II) rats. Chronic lung infection was established with alginate-embedded P. aeruginosa producing high amounts of beta-lactamase in 133 Lewis rats. Prior to infection, group I (66 rats) was immunized three...... times at 2-week intervals with purified beta-lactamase in incomplete Freund's adjuvant (IFA) and group II (67 rats) received IFA. Ceftazidime treatment was initiated after challenge and continued for 10 days, after which the rats were sacrificed and the lung bacteriology and pathology were analysed. Rat...

  12. Antibodies against beta-lactamase can improve ceftazidime treatment of lung infection with beta-lactam-resistant Pseudomonas aeruginosa in a rat model of chronic lung infection

    DEFF Research Database (Denmark)

    Ciofu, Oana; Bagge, Niels; Høiby, Niels

    2002-01-01

    times at 2-week intervals with purified beta-lactamase in incomplete Freund's adjuvant (IFA) and group II (67 rats) received IFA. Ceftazidime treatment was initiated after challenge and continued for 10 days, after which the rats were sacrificed and the lung bacteriology and pathology were analysed. Rat......To test the hypothesis that antibodies against the chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) might act as beta-lactamase inhibitors in patients with cystic fibrosis and chronic lung infection with P. aeruginosa, we compared in a rat model of chronic lung infection...... the efficacy of treatment with ceftazidime in beta-lactamase-immunized (group I) and non-immunized (group II) rats. Chronic lung infection was established with alginate-embedded P. aeruginosa producing high amounts of beta-lactamase in 133 Lewis rats. Prior to infection, group I (66 rats) was immunized three...

  13. Using multispectral imaging flow cytometry to assess an in vitro intracellular Burkholderia thailandensis infection model.

    Science.gov (United States)

    Jenner, Dominic; Ducker, Catherine; Clark, Graeme; Prior, Jo; Rowland, Caroline A

    2016-04-01

    The use of in vitro models to understand the interaction of bacteria with host cells is well established. In vitro bacterial infection models are often used to quantify intracellular bacterial load by lysing cell populations and subsequently enumerating the bacteria. Modern established techniques employ the use of fluorescence technologies such as flow cytometry, fluorescent microscopy, and/or confocal microscopy. However, these techniques often lack either the quantification of large data sets (microscopy) or use of gross fluorescence signal which lacks the visual confirmation that can provide additional confidence in data sets. Multispectral imaging flow cytometry (MIFC) is a novel emerging field of technology. This technology captures a bright field and fluorescence image of cells in a flow using a charged coupled device camera. It allows the analysis of tens of thousands of single cell images, making it an extremely powerful technology. Here MIFC was used as an alternative method of analyzing intracellular bacterial infection using Burkholderia thailandensis E555 as a model organism. It has been demonstrated that the data produced using traditional enumeration is comparable to data analyzed using MIFC. It has also been shown that by using MIFC it is possible to generate other data on the dynamics of the infection model rather than viable counts alone. It has been demonstrated that it is possible to inhibit the uptake of bacteria into mammalian cells and identify differences between treated and untreated cell populations. The authors believe this to be the first use of MIFC to analyze a Burkholderia bacterial species during intracellular infection. © 2016 Crown copyright. Published by Wiley Periodicals Inc. on behalf of ISAC. © 2015 International Society for Advancement of Cytometry.

  14. Chemotheraphy Efficiency of Phosphonium Heterocyclic Compounds with Pyrimidine Cycle in Models of Generalized Staph Infection

    Directory of Open Access Journals (Sweden)

    A.V. Humenna

    2016-02-01

    Full Text Available It was conducted the study of the effectiveness of chemotherapy with 2-phenyl-4-(1-pyrrolidinyl-6-izopropiltio-5-pyrimidyltriphenylphosphonium perchlorate, which refers to phosphonium heterocyclic compounds with pyrimidine cycle in the experiment on the model of generalized staph infection. The results were positive and they allow make a conclusion about the possibility of their use in clinical trials and develop promising antibacterial and antiseptic preparations on their basis.

  15. Evaluation of Mouse Wound Models for Probiotics-Based Wound Infection Prevention Study

    Science.gov (United States)

    2016-06-01

    infection. The cryo burn and skin incision with circulatory disruption models were not reproducible. Application of probiotic ( L . reuteri ) had some...were inoculated with 1 x 106 CFU P. aeruginosa, 5 x 105 CFU S. pyogenes, 5 x 106 CFU L . reuteri , or a combination of bacteria with the probiotic in...U ni ts /g T is su e L . reuteri Figure 1. Colonization of the wound site with probiotic. 6 DISTRIBUTION STATEMENT A. Approved for public release

  16. Infection-acquired versus vaccine-acquired immunity in an SIRWS model

    OpenAIRE

    Leung, Tiffany; Hughes, Barry D; Frascoli, Federico; Campbell, Patricia T; McCaw, James M

    2017-01-01

    Despite high vaccine coverage, pertussis has re-emerged as a public health concern in many countries. One hypothesis posed for re-emergence is the waning of immunity. In some disease systems, the process of waning immunity can be non-linear, involving a complex relationship between the duration of immunity and subsequent boosting of immunity through asymptomatic re-exposure. We present and analyse a model of infectious disease transmission to examine the interplay between infection and immuni...

  17. Numerical approximation for HIV infection of CD4+ T cells mathematical model

    Directory of Open Access Journals (Sweden)

    Vineet K. Srivastava

    2014-06-01

    Full Text Available A dynamical model of HIV infection of CD4+ T cells is solved numerically using an approximate analytical method so-called the differential transform method (DTM. The solution obtained by the method is an infinite power series for appropriate initial condition, without any discretization, transformation, perturbation, or restrictive conditions. A comparative study between the present method, the classical Euler’s and Runge–Kutta fourth order (RK4 methods is also carried out.

  18. The fitting of general force-of-infection models to wildlife disease prevalence data

    Science.gov (United States)

    Heisey, D.M.; Joly, D.O.; Messier, F.

    2006-01-01

    Researchers and wildlife managers increasingly find themselves in situations where they must deal with infectious wildlife diseases such as chronic wasting disease, brucellosis, tuberculosis, and West Nile virus. Managers are often charged with designing and implementing control strategies, and researchers often seek to determine factors that influence and control the disease process. All of these activities require the ability to measure some indication of a disease's foothold in a population and evaluate factors affecting that foothold. The most common type of data available to managers and researchers is apparent prevalence data. Apparent disease prevalence, the proportion of animals in a sample that are positive for the disease, might seem like a natural measure of disease's foothold, but several properties, in particular, its dependency on age structure and the biasing effects of disease-associated mortality, make it less than ideal. In quantitative epidemiology, the a??force of infection,a?? or infection hazard, is generally the preferred parameter for measuring a disease's foothold, and it can be viewed as the most appropriate way to a??adjusta?? apparent prevalence for age structure. The typical ecology curriculum includes little exposure to quantitative epidemiological concepts such as cumulative incidence, apparent prevalence, and the force of infection. The goal of this paper is to present these basic epidemiological concepts and resulting models in an ecological context and to illustrate how they can be applied to understand and address basic epidemiological questions. We demonstrate a practical approach to solving the heretofore intractable problem of fitting general force-of-infection models to wildlife prevalence data using a generalized regression approach. We apply the procedures to Mycobacterium bovis (bovine tuberculosis) prevalence in bison (Bison bison) in Wood Buffalo National Park, Canada, and demonstrate strong age dependency in the force of

  19. Two-spotted cricket as an animal infection model of human pathogenic fungi.

    Science.gov (United States)

    Kochi, Yuto; Matsumoto, Yasuhiko; Sekimizu, Kazuhisa; Kaito, Chikara

    2017-11-22

    Invertebrate infection models that can be evaluated at human body temperature are limited. In this study, we utilized the two-spotted cricket, a heat-tolerant insect, as an animal infection model of human pathogenic fungi. Injection of human pathogenic fungi, including Candida albicans, Candida glabrata, and Cryptococcus neoformans killed crickets within 48 h at both 27˚C and 37˚C. The median lethal dose values (LD50 values) of C. albicans and C. glabrata against crickets were decreased at 37˚C compared to that at 27˚C, whereas the LD50 value of C. neoformans was not different between 27˚C and 37˚C. Heat-killed cells of the three different fungi also killed crickets, but the LD50 value of the heat-killed cells was higher than 5-fold that of live fungal cells in the respective species. C. neoformans gene-knockout strains of cna1, gpa1, and pka1, which are required for virulence in mammals, had greater LD50 values than the parent strain in crickets. These findings suggest that the two-spotted cricket is a valuable infection model of human pathogenic fungi that can be used to evaluate fungal virulence at variable temperatures, including 37˚C, and that the killing abilities of C. albicans and C. glabrata against animals are increased at 37˚C.

  20. Humanized mouse models to study pathophysiology and treatment of HIV infection.

    Science.gov (United States)

    Masse-Ranson, Guillemette; Mouquet, Hugo; Di Santo, James P

    2018-03-01

    Immunodeficient mice that lack all lymphocyte subsets and have phagocytic cells that are tolerant of human cells can be stably xenografted with human hematopoietic stem cell as well as other human tissues (fetal liver and thymus) creating 'human immune system' (HIS) mice. HIS mice develop all major human lymphocyte classes (B, T, natural killer, and innate lymphoid cell) and their specialized subsets as well as a variety of myeloid cells (dendritic cell, monocytes, and macrophages) thereby providing a small animal model in which to interrogate human immune responses to infection. HIS mouse models have been successfully used to study several aspects of HIV-1 biology, including viral life cycle (entry, restriction, replication, and spread) as well as virus-induced immunopathology (CD4 T-cell depletion, immune activation, and mucosal inflammation). Recent work has shown that HIV reservoirs can be established in HIV-infected HIS mice after treatment with combinations of antiretroviral drugs thereby providing a model to test new approaches to eliminate latently infected cells. HIS mice provide cost-effective preclinical platform to assess combination immunotherapies that can target HIV reservoirs. Therapeutic strategies validated in HIS mice should be considered in designing the roadmap toward HIV 'cure'.

  1. Domestic Pig (Sus scrofa) as an Animal Model for Experimental Trypanosoma cruzi Infection

    Science.gov (United States)

    Yauri, Verónica; Castro-Sesquen, Yagahira E.; Verastegui, Manuela; Angulo, Noelia; Recuenco, Fernando; Cabello, Ines; Malaga, Edith; Bern, Caryn; Gavidia, Cesar M.; Gilman, Robert H.

    2016-01-01

    Pigs were infected with a Bolivian strain of Trypanosoma cruzi (genotype I) and evaluated up to 150 days postinoculation (dpi) to determine the use of pigs as an animal model of Chagas disease. Parasitemia was observed in the infected pigs during the acute phase (15–40 dpi). Anti-T.cruzi immunoglobulin M was detected during 15–75 dpi; high levels of anti-T.cruzi immunoglobulin G were detected in all infected pigs from 75 to 150 dpi. Parasitic DNA was observed by western blot (58%, 28/48) and polymerase chain reaction (27%, 13/48) in urine samples, and in the brain (75%, 3/4), spleen (50%, 2/4), and duodenum (25%, 1/4), but no parasitic DNA was found in the heart, colon, and kidney. Parasites were not observed microscopically in tissues samples, but mild inflammation, vasculitis, and congestion was observed in heart, brain, kidney, and spleen. This pig model was useful for the standardization of the urine test because of the higher volume that can be obtained as compared with other small animal models. However, further experiments are required to observe pathological changes characteristic of Chagas disease in humans. PMID:26928841

  2. Global Stability of Delayed Viral Infection Models with Nonlinear Antibody and CTL Immune Responses and General Incidence Rate

    OpenAIRE

    Miao, Hui; Teng, Zhidong; Li, Zhiming

    2016-01-01

    The dynamical behaviors for a five-dimensional viral infection model with three delays which describes the interactions of antibody, cytotoxic T-lymphocyte (CTL) immune responses, and nonlinear incidence rate are investigated. The threshold values for viral infection, antibody response, CTL immune response, CTL immune competition, and antibody competition, respectively, are established. Under certain assumptions, the threshold value conditions on the global stability of the infection-free, im...

  3. Mixed infections with Chlamydia and porcine epidemic diarrhea virus - a new in vitro model of chlamydial persistence.

    Science.gov (United States)

    Borel, Nicole; Dumrese, Claudia; Ziegler, Urs; Schifferli, Andrea; Kaiser, Carmen; Pospischil, Andreas

    2010-07-27

    Chlamydiae induce persistent infections, which have been associated with a wide range of chronic diseases in humans and animals. Mixed infections with Chlamydia and porcine epidemic diarrhea virus (PEDV) may result in generation of persistent chlamydial infections. To test this hypothesis, an in vitro model of dual infection with cell culture-adapted PEDV and Chlamydia abortus or Chlamydia pecorum in Vero cells was established. Infected cultures were investigated by immunofluorescence (IF), transmission electron microscopy (TEM) and re-infection experiments. By IF, Chlamydia-infected cells showed normal inclusions after 39 hpi. Dual infections with Chlamydia abortus revealed a heterogenous mix of inclusion types including small inclusions consisting of aberrant bodies (ABs), medium-sized inclusions consisting of ABs and reticulate bodies and normal inclusions. Only aberrant inclusions were observable in dual infection experiments with Chlamydia pecorum and PEDV. TEM examinations of mixed infections with Chlamydia abortus and Chlamydia pecorum revealed aberrant chlamydial inclusions containing reticulate-like, pleomorphic ABs, which were up to 2 microm in diameter. No re-differentiation into elementary bodies (EBs) was detected. In re-infection experiments, co-infected cells produced fewer EBs than monoinfected cells. In the present study we confirm that PEDV co-infection alters the developmental cycle of member species of the family Chlamydiaceae, in a similar manner to other well-described persistence induction methods. Interestingly, this effect appears to be partially species-specific as Chlamydia pecorum appears more sensitive to PEDV co-infection than Chlamydia abortus, as evidenced by TEM and IF observations of a homogenous population of aberrant inclusions in PEDV - Chlamydia pecorum co-infections.

  4. Mixed infections with Chlamydia and porcine epidemic diarrhea virus - a new in vitro model of chlamydial persistence

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    Kaiser Carmen

    2010-07-01

    Full Text Available Abstract Background Chlamydiae induce persistent infections, which have been associated with a wide range of chronic diseases in humans and animals. Mixed infections with Chlamydia and porcine epidemic diarrhea virus (PEDV may result in generation of persistent chlamydial infections. To test this hypothesis, an in vitro model of dual infection with cell culture-adapted PEDV and Chlamydia abortus or Chlamydia pecorum in Vero cells was established. Results Infected cultures were investigated by immunofluorescence (IF, transmission electron microscopy (TEM and re-infection experiments. By IF, Chlamydia-infected cells showed normal inclusions after 39 hpi. Dual infections with Chlamydia abortus revealed a heterogenous mix of inclusion types including small inclusions consisting of aberrant bodies (ABs, medium-sized inclusions consisting of ABs and reticulate bodies and normal inclusions. Only aberrant inclusions were observable in dual infection experiments with Chlamydia pecorum and PEDV. TEM examinations of mixed infections with Chlamydia abortus and Chlamydia pecorum revealed aberrant chlamydial inclusions containing reticulate-like, pleomorphic ABs, which were up to 2 μm in diameter. No re-differentiation into elementary bodies (EBs was detected. In re-infection experiments, co-infected cells produced fewer EBs than monoinfected cells. Conclusions In the present study we confirm that PEDV co-infection alters the developmental cycle of member species of the family Chlamydiaceae, in a similar manner to other well-described persistence induction methods. Interestingly, this effect appears to be partially species-specific as Chlamydia pecorum appears more sensitive to PEDV co-infection than Chlamydia abortus, as evidenced by TEM and IF observations of a homogenous population of aberrant inclusions in PEDV - Chlamydia pecorum co-infections.

  5. hlorhexidine-releasing implant coating on intramedullary nail reduces infection in a rat model

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    SM Shiels

    2018-05-01

    Full Text Available The use of internal intramedullary nails for long bone fracture fixation is a common practice among surgeons. Bacteria naturally attach to these devices, increasing the risk for wound infection, which can result in non- or malunion, additional surgical procedures and extended hospital stays. Intramedullary nail surface properties can be modified to reduce bacterial colonisation and potentially infectious complications. In the current study, a coating combining a non-fouling property with leaching chlorhexidine for orthopaedic implantation was tested. Coating stability and chlorhexidine release were evaluated in vitro. Using a rat model of intramedullary fixation and infection, the effect of the coating on microbial colonisation and fracture healing was evaluated in vivo by quantitative microbiology, micro-computed tomography, plain radiography, three-point bending and/or histology. Low dose systemic cefazolin was administered to increase the similarities to clinical practice, without overshadowing the effect of the anti-infective coating. When introduced into a contaminated wound, the non-fouling chlorhexidine-coated implant reduced the overall bacteria colonisation within the bone and on the implant, reduced the osteolysis and increased the radiographic union, confirming its potential for reducing complications in wounds at high risk of infection. However, when implanted into a sterile wound, non-union increased. Further studies are required to best optimise the anti-microbial effectiveness, while not sacrificing fracture union.

  6. An Epidemic Model of Computer Worms with Time Delay and Variable Infection Rate

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    Yu Yao

    2018-01-01

    Full Text Available With rapid development of Internet, network security issues become increasingly serious. Temporary patches have been put on the infectious hosts, which may lose efficacy on occasions. This leads to a time delay when vaccinated hosts change to susceptible hosts. On the other hand, the worm infection is usually a nonlinear process. Considering the actual situation, a variable infection rate is introduced to describe the spread process of worms. According to above aspects, we propose a time-delayed worm propagation model with variable infection rate. Then the existence condition and the stability of the positive equilibrium are derived. Due to the existence of time delay, the worm propagation system may be unstable and out of control. Moreover, the threshold τ0 of Hopf bifurcation is obtained. The worm propagation system is stable if time delay is less than τ0. When time delay is over τ0, the system will be unstable. In addition, numerical experiments have been performed, which can match the conclusions we deduce. The numerical experiments also show that there exists a threshold in the parameter a, which implies that we should choose appropriate infection rate β(t to constrain worm prevalence. Finally, simulation experiments are carried out to prove the validity of our conclusions.

  7. 3D Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent VZV Infection

    Science.gov (United States)

    Goodwin, Thomas J.

    2013-01-01

    Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.

  8. System Dynamics based Dengue modeling environment to simulate evolution of Dengue infection under different climate scenarios

    Science.gov (United States)

    Anwar, R.; Khan, R.; Usmani, M.; Colwell, R. R.; Jutla, A.

    2017-12-01

    Vector borne infectious diseases such as Dengue, Zika and Chikungunya remain a public health threat. An estimate of the World Health Organization (WHO) suggests that about 2.5 billion people, representing ca. 40% of human population,are at increased risk of dengue; with more than 100 million infection cases every year. Vector-borne infections cannot be eradicated since disease causing pathogens survive in the environment. Over the last few decades dengue infection has been reported in more than 100 countries and is expanding geographically. Female Ae. Aegypti mosquito, the daytime active and a major vector for dengue virus, is associated with urban population density and regional climatic processes. However, mathematical quantification of relationships on abundance of vectors and climatic processes remain a challenge, particularly in regions where such data are not routinely collected. Here, using system dynamics based feedback mechanism, an algorithm integrating knowledge from entomological, meteorological and epidemiological processes is developed that has potential to provide ensemble simulations on risk of occurrence of dengue infection in human population. Using dataset from satellite remote sensing, the algorithm was calibrated and validated using actual dengue case data of Iquitos, Peru. We will show results on model capabilities in capturing initiation and peak in the observed time series. In addition, results from several simulation scenarios under different climatic conditions will be discussed.

  9. Evaluation of a nonsteroidal topical cream in a guinea pig model of Malassezia furfur infection.

    Science.gov (United States)

    Nalamothu, Vijendra; O'Leary, Ann L; Kandavilli, Sateesh; Fraser, Joanne; Pandya, Vishvabhavan

    2009-01-01

    Malassezia furfur is an important causal factor for seborrheic dermatitis, and topical antifungal therapy is an effective treatment approach. This study assessed the antifungal activity of Promiseb Topical Cream (Promius Pharma, LLC, Bridgewater, NJ), a novel nonsteroidal prescription medical device cream, in the M furfur-infected skin model for guinea pigs. Guinea pigs (N = 28) were divided into 4 groups and infected with M furfur for 7 days. On day 8, the first group of animals was sacrificed. The scrapings of inoculation site on each animal were tested for the presence of the organism, and the skin was excised for quantitation of M furfur. The second group was left untreated. The remaining 2 groups were treated with one of the test agents (Promiseb) and the positive control product (ciclopirox olamine cream, 0.77%; Loprox, Medicis, Scottsdale, AZ) each once daily for 3 days. At the end of treatment, animals were sacrificed and analyzed similarly to the first group. M furfur was recovered from all animals in the first group. Visual signs of infection, such as erythema and edema, were not observed in the infected animals at the end of the study. In the animals treated for 3 days with the test agents, the M furfur counts were reduced to below the limit of quantitation. Both test agents were equally effective in substantially reducing the density of M furfur compared with the untreated control.

  10. Stability of a general delayed virus dynamics model with humoral immunity and cellular infection

    Science.gov (United States)

    Elaiw, A. M.; Raezah, A. A.; Alofi, A. S.

    2017-06-01

    In this paper, we investigate the dynamical behavior of a general nonlinear model for virus dynamics with virus-target and infected-target incidences. The model incorporates humoral immune response and distributed time delays. The model is a four dimensional system of delay differential equations where the production and removal rates of the virus and cells are given by general nonlinear functions. We derive the basic reproduction parameter R˜0 G and the humoral immune response activation number R˜1 G and establish a set of conditions on the general functions which are sufficient to determine the global dynamics of the models. We use suitable Lyapunov functionals and apply LaSalle's invariance principle to prove the global asymptotic stability of the all equilibria of the model. We confirm the theoretical results by numerical simulations.

  11. A virtual infection model quantifies innate effector mechanisms and Candida albicans immune escape in human blood.

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    Kerstin Hünniger

    2014-02-01

    Full Text Available Candida albicans bloodstream infection is increasingly frequent and can result in disseminated candidiasis associated with high mortality rates. To analyze the innate immune response against C. albicans, fungal cells were added to human whole-blood samples. After inoculation, C. albicans started to filament and predominantly associate with neutrophils, whereas only a minority of fungal cells became attached to monocytes. While many parameters of host-pathogen interaction were accessible to direct experimental quantification in the whole-blood infection assay, others were not. To overcome these limitations, we generated a virtual infection model that allowed detailed and quantitative predictions on the dynamics of host-pathogen interaction. Experimental time-resolved data were simulated using a state-based modeling approach combined with the Monte Carlo method of simulated annealing to obtain quantitative predictions on a priori unknown transition rates and to identify the main axis of antifungal immunity. Results clearly demonstrated a predominant role of neutrophils, mediated by phagocytosis and intracellular killing as well as the release of antifungal effector molecules upon activation, resulting in extracellular fungicidal activity. Both mechanisms together account for almost [Formula: see text] of C. albicans killing, clearly proving that beside being present in larger numbers than other leukocytes, neutrophils functionally dominate the immune response against C. albicans in human blood. A fraction of C. albicans cells escaped phagocytosis and remained extracellular and viable for up to four hours. This immune escape was independent of filamentation and fungal activity and not linked to exhaustion or inactivation of innate immune cells. The occurrence of C. albicans cells being resistant against phagocytosis may account for the high proportion of dissemination in C. albicans bloodstream infection. Taken together, iterative experiment-model

  12. Establishment of animal model for Echinococcus inoculation infection in Microtus fuscus in Qinghai-Tibet Plateau

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    WANG Zhan

    2018-02-01

    Full Text Available ObjectiveTo analyze whether Microtus fuscus in Qinghai-Tibet Plateau can be used as an animal model for Echinococcus infection. MethodsSixty wild voles (Microtus fuscus were equally divided into groups A, B, and C to undergo Echinococcus inoculation through subcutaneous injection, direct transhepatic approach, and percutaneous transhepatic approach, respectively. Three months later, the infection rate and mortality rate were determined. After the model animals were sacrificed, HE staining was performed for the infiltration zone of lesion (2-3 mm near the lesion, the area adjacent to the lesion and 50% of the lesion, the center of lesion (non-liquefied area, the liquefied area of lesion, the margin of lesion (not including the normal tissue, and 70% of the lesion, and the pathological structures of hydatid lesions were observed under a microscope. Protoscoleces were extracted from the lesions for in vitro culture. The chi-square test was used for comparison of categorical data. ResultsThe success rate of Echinococcus infection in groups A, B, and C were 60%, 80%, and 70%, respectively, with no significant difference between the three groups (χ2=4.138, P=0.126. The mortality rates of groups A, B, and C were 5%, 20%, and 15%, respectively, with no significant difference between the three groups (χ2=5.201, P=0.107. HE staining showed that the red-stained vesicles had thin, discontinuous cuticular layers, with massive inflammatory cell infiltration around the vesicles; no protoscoleces were observed in all sections. After in vitro culture and staining of the lesion tissue, a large number of live protoscoleces were observed, unstained and with motility. ConclusionThis study confirms that Microtus fuscus, an endemic species in Qinghai-Tibet Plateau, can be used as an animal model for Echinococcus infection. Subcutaneous injection is an appropriate method for Echinococcus inoculation.

  13. Syrian Hamster as an Animal Model for the Study of Human Influenza Virus Infection.

    Science.gov (United States)

    Iwatsuki-Horimoto, Kiyoko; Nakajima, Noriko; Ichiko, Yurie; Sakai-Tagawa, Yuko; Noda, Takeshi; Hasegawa, Hideki; Kawaoka, Yoshihiro

    2018-02-15

    Ferrets and mice are frequently used as animal models for influenza research. However, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza A or B viruses. Therefore, prior adaptation of human viruses is required for their use in mice. In addition, there are no mouse-adapted variants of the recent H3N2 viruses, because these viruses do not replicate well in mice. In this study, we investigated the susceptibility of Syrian hamsters to influenza viruses with a view to using the hamster model as an alternative to the mouse model. We found that hamsters are sensitive to influenza viruses, including the recent H3N2 viruses, without adaptation. Although the hamsters did not show weight loss or clinical signs of H3N2 virus infection, we observed pathogenic effects in the respiratory tracts of the infected animals. All of the H3N2 viruses tested replicated in the respiratory organs of the hamsters, and some of them were detected in the nasal washes of infected animals. Moreover, a 2009 pandemic (pdm09) virus and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were transmissible by the airborne route in these hamsters. Hamsters thus have the potential to be a small-animal model for the study of influenza virus infection, including studies of the pathogenicity of H3N2 viruses and other strains, as well as for use in H1N1 virus transmission studies. IMPORTANCE We found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 virus and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested, are transmitted by the airborne route in these hamsters. Syrian hamsters thus have the potential to be used as a small-animal model for the study of human influenza viruses. Copyright © 2018 American Society for Microbiology.

  14. Encapsulation of antigen-loaded silica nanoparticles into microparticles for intradermal powder injection.

    Science.gov (United States)

    Deng, Yibin; Mathaes, Roman; Winter, Gerhard; Engert, Julia

    2014-10-15

    Epidermal powder immunisation (EPI) is being investigated as a promising needle-free delivery methods for vaccination. The objective of this work was to prepare a nanoparticles-in-microparticles (nano-in-micro) system, integrating the advantages of nanoparticles and microparticles into one vaccine delivery system for epidermal powder immunisation. Cationic mesoporous silica nanoparticles (MSNP-NH2) were prepared and loaded with ovalbumin as a model antigen. Loading was driven by electrostatic interactions. Ovalbumin-loaded silica nanoparticles were subsequently formulated into sugar-based microparticles by spray-freeze-drying. The obtained microparticles meet the size requirement for EPI. Confocal microscopy was used to demonstrate that the nanoparticles are homogeneously distributed in the microparticles. Furthermore, the silica nanoparticles in the dry microparticles can be re-dispersed in aqueous solution showing no aggregation. The recovered ovalbumin shows integrity compared to native ovalbumin. The present nano-in-micro system allows (1) nanoparticles to be immobilized and finely distributed in microparticles, (2) microparticle formation and (3) re-dispersion of nanoparticles without subsequent aggregation. The nanoparticles inside microparticles can (1) adsorb proteins to cationic shell/surface voids in spray-dried products without detriment to ovalbumin stability, (2) deliver antigens in nano-sized modes to allow recognition by the immune system. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Analysis of Schistosomiasis haematobium infection prevalence and intensity in Chikhwawa, Malawi: an application of a two part model.

    Science.gov (United States)

    Chipeta, Michael G; Ngwira, Bagrey; Kazembe, Lawrence N

    2013-01-01

    Urinary Schistosomiasis infection, a common cause of morbidity especially among children in less developed countries, is measured by the number of eggs per urine. Typically a large proportion of individuals are non-egg excretors, leading to a large number of zeros. Control strategies require better understanding of its epidemiology, hence appropriate methods to model infection prevalence and intensity are crucial, particularly if such methods add value to targeted implementation of interventions. We consider data that were collected in a cluster randomized study in 2004 in Chikhwawa district, Malawi, where eighteen (18) villages were selected and randomised to intervention and control arms. We developed a two-part model, with one part for analysis of infection prevalence and the other to model infection intensity. In both parts of the model we adjusted for age, sex, education level, treatment arm, occupation, and poly-parasitism. We also assessed for spatial correlation in the model residual using variogram analysis and mapped the spatial variation in risk. The model was fitted using maximum likelihood estimation. The study had a total of 1642 participants with mean age of 32.4 (Standard deviation: 22.8), of which 55.4 % were female. Schistosomiasis prevalence was 14.2 %, with a large proportion of individuals (85.8 %) being non-egg excretors, hence zero-inflated data. Our findings showed that S. haematobium was highly localized even after adjusting for risk factors. Prevalence of infection was low in males as compared to females across all the age ranges. S. haematobium infection increased with presence of co-infection with other parasite infection. Infection intensity was highly associated with age; with highest intensity in school-aged children (6 to 15 years). Fishing and working in gardens along the Shire River were potential risk factors for S. haematobium infection intensity. Intervention reduced both infection intensity and prevalence in the intervention

  16. A modeling study of human infections with avian influenza A H7N9 virus in mainland China

    Directory of Open Access Journals (Sweden)

    Zhifei Liu

    2015-12-01

    Conclusions: Screening and culling infected poultry is a critical measure for preventing human H7N9 infections in the long term. This model may provide important insights for decision-making on a national intervention strategy for the long-term control of the H7N9 virus epidemic.

  17. Antifungal Efficacy during Candida krusei Infection in Non-Conventional Models Correlates with the Yeast In Vitro Susceptibility Profile

    Science.gov (United States)

    Scorzoni, Liliana; de Lucas, Maria Pilar; Mesa-Arango, Ana Cecilia; Fusco-Almeida, Ana Marisa; Lozano, Encarnación; Cuenca-Estrella, Manuel; Mendes-Giannini, Maria Jose; Zaragoza, Oscar

    2013-01-01

    The incidence of opportunistic fungal infections has increased in recent decades due to the growing proportion of immunocompromised patients in our society. Candida krusei has been described as a causative agent of disseminated fungal infections in susceptible patients. Although its prevalence remains low among yeast infections (2–5%), its intrinsic resistance to fluconazole makes this yeast important from epidemiologic aspects. Non mammalian organisms are feasible models to study fungal virulence and drug efficacy. In this work we have used the lepidopteran Galleria mellonella and the nematode Caenorhabditis elegans as models to assess antifungal efficacy during infection by C. krusei. This yeast killed G. mellonella at 25, 30 and 37°C and reduced haemocytic density. Infected larvae melanized in a dose-dependent manner. Fluconazole did not protect against C. krusei infection, in contrast to amphotericin B, voriconazole or caspofungin. However, the doses of these antifungals required to obtain larvae protection were always higher during C. krusei infection than during C. albicans infection. Similar results were found in the model host C. elegans. Our work demonstrates that non mammalian models are useful tools to investigate in vivo antifungal efficacy and virulence of C. krusei. PMID:23555877

  18. Optimization and characterization of a murine lung infection model for the evaluation of novel therapeutics against Burkholderia cenocepacia.

    Science.gov (United States)

    Vanhoutte, Bieke; Cappoen, Davie; Maira, Bidart de Macedo; Cools, Freya; Torfs, Eveline; Coenye, Tom; Martinet, Wim; Caljon, Guy; Maes, Louis; Delputte, Peter; Cos, Paul

    2017-08-01

    Several B. cenocepacia mouse models are available to study the pulmonary infection by this Burkholderia cepacia complex (BCC) species. However, a characterized B. cenocepacia mouse model to evaluate the efficacy of potential new antibacterial therapies is not yet described. Therefore, we optimized and validated the course of infection (i.e. bacterial proliferation in lung, liver and spleen) and the efficacy of a reference antibiotic, tobramycin (TOB), in a mouse lung infection model. Furthermore, the local immune response and histological changes in lung tissue were studied during infection and treatment. A reproducible lung infection was observed when immunosuppressed BALB/c mice were infected with B. cenocepacia LMG 16656. Approximately 50 to 60% of mice infected with this BCC species demonstrated a dissemination to liver and spleen. TOB treatment resulted in a two log reduction in lung burden, prevented dissemination of B. cenocepacia to liver and spleen and significantly reduced levels of proinflammatory cytokines. As this mouse model is characterized by a reproducible course of infection and efficacy of TOB, it can be used as a tool for the in vivo evaluation of new antibacterial therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. The effect of education based on health belief model on health beliefs of women with urinary tract infection.

    Science.gov (United States)

    Javaheri Tehrani, Fereshteh; Nikpour, Soqra; Haji Kazemi, Eftekhar Alsadat; Sanaie, Neda; Shariat Panahi, Shabnam Alsadat

    2014-01-01

    Urinary Tract Infection is one of the commonest infections which affect humans. Half of all women have a UTI in their lifetime and one fourth have recurrent infections. Health behaviours can help patients to prevent Urinary Tract Infection recurrence and changing beliefs is necessary for health behaviour change. The aim of this study is to investigate the effect of education based on Health Belief Model on health beliefs of women with Urinary Tract Infection. This is a quasi-experimental study with pre-test and post-test design, conducted on 170 married women with Urinary Tract Infection, referred to selected hospital laboratories in Tehran. The laboratories were divided to experience and control groups. The data collection tool was a "self-administrated" questionnaire which was answered by samples of both groups, prior to the intervention and 12 weeks thereafter. The intervention (education based on Health Belief Model) was performed on the experiment group. Based on the study results, after the intervention the average score of the perceived susceptibility (Phealth behaviours (PHealth Belief Model was effective in promoting the health beliefs (except perceived barriers) and health behaviours of women with Urinary Tract Infection. Therefore, it can be suggested that the mentioned model can be used as one of the strategies for prevention of Urinary Tract Infection in women.

  20. A stochastic model of latently infected cell reactivation and viral blip generation in treated HIV patients.

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    Jessica M Conway

    2011-04-01

    Full Text Available Motivated by viral persistence in HIV+ patients on long-term anti-retroviral treatment (ART, we present a stochastic model of HIV viral dynamics in the blood stream. We consider the hypothesis that the residual viremia in patients on ART can be explained principally by the activation of cells latently infected by HIV before the initiation of ART and that viral blips (clinically-observed short periods of detectable viral load represent large deviations from the mean. We model the system as a continuous-time, multi-type branching process. Deriving equations for the probability generating function we use a novel numerical approach to extract the probability distributions for latent reservoir sizes and viral loads. We find that latent reservoir extinction-time distributions underscore the importance of considering reservoir dynamics beyond simply the half-life. We calculate blip amplitudes and frequencies by computing complete viral load probability distributions, and study the duration of viral blips via direct numerical simulation. We find that our model qualitatively reproduces short small-amplitude blips detected in clinical studies of treated HIV infection. Stochastic models of this type provide insight into treatment-outcome variability that cannot be found from deterministic models.

  1. Safety and immunogenicity of a new purified vero cell rabies vaccine (PVRV) administered by intramuscular and intradermal routes in healthy volunteers.

    Science.gov (United States)

    Kulkarni, Prasad S; Sapru, Amita; D'costa, Pradeep M; Pandit, Anand; Madhusudana, Shampur N; Yajaman, Ashwin Belludi; Mangrule, Somnath; Gunale, Bhagwat; Bavdekar, Ashish R

    2013-05-31

    Rabies is 100% fatal but preventable with modern vaccines and immunoglobulins. There is a huge demand for rabies vaccines in developing countries of Asia and Africa. We have developed a new purified vero cell rabies vaccine (PVRV) and evaluated its safety and immunogenicity in healthy volunteers by intramuscular (IM) and intradermal (ID) routes of vaccination. Sixty adults aged between 18 and 50 years were recruited in this actively controlled Phase I clinical study and were randomized to receive three 1 ml or 0.1 ml doses of new PVRV intramuscularly or intradermally on days 0, 7 and 21. The control group received commercially available PVRV (Verorab) by intramuscular route. Adverse events (AEs) were recorded with diary cards till day 28 post-vaccination. Immunogenicity was assessed on day 0, 7, 21 and 42 by rapid fluorescence focus inhibition test (RFFIT). In all, 116 solicited local and systemic events were reported across the three groups. Most were mild and resolved without sequelae. Also the few unsolicited events, deemed unrelated to the study vaccines, caused no problems. No significant changes in the routine laboratory parameters were found. Two doses of a vaccine elicited protective titres (≥ 0.5 IU/ml) in all subjects, the GMTs varying between 0.57 and 0.69 IU/ml on day 7, 3.07 and 3.97 IU/ml on day 21, and 6.12 and 8.52 IU/ml on day 42 post-vaccination. PVRV was well tolerated and showed good immunogenicity regardless of whether administered intramuscularly or, using a tenth of that volume, intradermally. Further studies with this new vaccine are warranted. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Comparison of the intradermal irritant threshold concentrations of nine allergens from two different manufacturers in clinically nonallergic dogs in the USA.

    Science.gov (United States)

    Foust-Wheatcraft, Desirae A; Dell, Darin L; Rosenkrantz, Wayne S; Griffin, Craig E

    2017-12-01

    The intradermal irritant threshold concentration for many allergens is unknown. To determine the intradermal irritant threshold concentration (ITC) of nine allergens from two different manufacturers. Twenty privately owned clinically nonallergic dogs. Alternaria, cat dander, Dermatophagoides farinae, Chenopodium album (lamb's quarter), Xanthium strumarium (cocklebur), Prosopis glandulosa (mesquite), Morus alba (white mulberry), Cynodon dactylon (Bermuda grass) and Phleum pretense (Timothy grass) from two manufacturers (ALK; Round Rock, TX, USA and Greer ® Laboratories; Lenoir, NC, USA) were injected intradermally at two dilutions and at 15 and 30 min evaluated subjectively (1-4) and objectively (horizontal wheal diameter) by two blinded investigators. A subjective score of 3 or 4 by either investigator at either timed reading was considered positive. If both concentrations resulted in positive reactions, two additional dilutions were performed. The ITC was defined as the lowest tested concentration that elicited a positive reaction in ≥10% of animals. The ITCs were Alternaria >2,000 PNU/mL; cat dander 750 PNU/mL (ALK) and 2,000 PNU/mL (Greer ® ); D. farinae glandulosa <500 PNU/mL; M. alba <6,000 PNU/mL; C. dactylon <10,000 PNU/mL (ALK) and <6,000 PNU/mL (Greer ® ); and P. pretense <6,000 PNU/mL. There were significant differences in subjective scoring and objective measurement between manufacturers for Alternaria, cat dander and P. pretense. Results revealed significant positive correlation between subjective scoring and objective measurement for each time, investigator and manufacturer separately. © 2017 ESVD and ACVD.

  3. Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Aerosolized Monkeypox Virus

    Science.gov (United States)

    2010-09-01

    routes, vaccinia virus or rabbitpox virus in rabbits by intradermal (i.d.) or aerosol routes, monkeypox virus in dormice, prairie dogs or ground...occurring most commonly in the African Congo [35]. An outbreak of human monkeypox occurred in the Midwestern US in 2003 after contact with prairie dogs ...lactate from tissues. Lactate is the end product when anaerobic glycolysis occurs in low oxygen conditions. Increased LDH in MPX infection indicates

  4. Modeling new immunoregulatory therapeutics as antimicrobial alternatives for treating Clostridium difficile infection.

    Science.gov (United States)

    Leber, Andrew; Hontecillas, Raquel; Abedi, Vida; Tubau-Juni, Nuria; Zoccoli-Rodriguez, Victoria; Stewart, Caroline; Bassaganya-Riera, Josep

    2017-05-01

    The current treatment paradigm in Clostridium difficile infection is the administration of antibiotics contributing to the high rates of recurrent infections. Recent alternative strategies, such as fecal microbiome transplantation and anti-toxin antibodies, have shown similar efficacy in the treatment of C. difficile associated disease (CDAD). However, barriers exist for either treatment or other novel treatments to displace antibiotics as the standard of care. To aid in the comparison of these and future treatments in CDAD, we developed an in silico pipeline to predict clinical efficacy with nonclinical results. The pipeline combines an ordinary differential equation (ODE)-based model, describing the immunological and microbial interactions in the gastrointestinal (GI) mucosa, with machine learning algorithms to translate simulated output quantities (i.e. time of clearance, quantity of commensal bacteria, T cell ratios) into clinical predictions based on prior preclinical, translational and clinical trial data. As a use case, we compare the efficacy of lanthionine synthetase C-like 2 (LANCL2), a novel immunoregulatory target with promising efficacy in inflammatory bowel disease (IBD), activation with antibiotics, fecal microbiome transplantation and anti-toxin antibodies in the treatment of CDAD. We further validate the potential of LANCL2 pathway activation, in a mouse model of C. difficile infection in which it displays an ability to decrease weight loss and inflammatory cell types while protecting against mortality. The computational pipeline can serve as an important resource in the development of new treatment modalities. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Fabric-skin models to assess infection transfer for impetigo contagiosa in a kindergarten scenario.

    Science.gov (United States)

    Gerhardts, A; Henze, S V; Bockmühl, D; Höfer, D

    2015-06-01

    Children in community bodies like kindergartens are predisposed to suffer from impetigo. To consider important measures for infection prevention, direct and indirect transmission routes of pathogens must be revealed. Therefore, we studied the role of skin and fabrics in the spread of the impetigo pathogen Staphylococcus aureus and the strain Streptococcus equi (surrogate to Streptococcus pyogenes) in order to assess infection transfer in realistic scenarios. The transmission of test strains was studied with standardized fabric-skin models using a technical artificial skin and fabrics of different fiber types commonly occurring in German kindergartens. In synthetic pus, both test strains persisted on artificial skin and fabrics for at least 4 h. Friction enhanced transfer, depending on the fiber type or fabric construction. In a skin-to-skin setup, the total transfer was higher than via fabrics and no decrease in the transmission rates from donor to recipients could be observed after successive direct skin contacts. Children in kindergartens may be at risk of transmission for impetigo pathogens, especially via direct skin contact, but also by the joint use of fabrics, like towels or handicraft materials. Fabric-skin models used in this study enable further insight into the transmission factors for skin infections on the basis of a practical approach.

  6. Mapping the potential risk of mycetoma infection in Sudan and South Sudan using ecological niche modeling.

    Science.gov (United States)

    Samy, Abdallah M; van de Sande, Wendy W J; Fahal, Ahmed Hassan; Peterson, A Townsend

    2014-10-01

    In 2013, the World Health Organization (WHO) recognized mycetoma as one of the neglected tropical conditions due to the efforts of the mycetoma consortium. This same consortium formulated knowledge gaps that require further research. One of these gaps was that very few data are available on the epidemiology and transmission cycle of the causative agents. Previous work suggested a soil-borne or Acacia thorn-prick-mediated origin of mycetoma infections, but no studies have investigated effects of soil type and Acacia geographic distribution on mycetoma case distributions. Here, we map risk of mycetoma infection across Sudan and South Sudan using ecological niche modeling (ENM). For this study, records of mycetoma cases were obtained from the scientific literature and GIDEON; Acacia records were obtained from the Global Biodiversity Information Facility. We developed ENMs based on digital GIS data layers summarizing soil characteristics, land-surface temperature, and greenness indices to provide a rich picture of environmental variation across Sudan and South Sudan. ENMs were calibrated in known endemic districts and transferred countrywide; model results suggested that risk is greatest in an east-west belt across central Sudan. Visualizing ENMs in environmental dimensions, mycetoma occurs under diverse environmental conditions. We compared niches of mycetoma and Acacia trees, and could not reject the null hypothesis of niche similarity. This study revealed contributions of different environmental factors to mycetoma infection risk, identified suitable environments and regions for transmission, signaled a potential mycetoma-Acacia association, and provided steps towards a robust risk map for the disease.

  7. A Mathematical Model Of Dengue-Chikungunya Co-Infection In A Closed Population

    Science.gov (United States)

    Aldila, Dipo; Ria Agustin, Maya

    2018-03-01

    Dengue disease has been a major health problem in many tropical and sub-tropical countries since the early 1900s. On the other hand, according to a 2017 WHO fact sheet, Chikungunya was detected in the first outbreak in 1952 in Tanzania and has continued increasing until now in many tropical and sub-tropical countries. Both these diseases are vector-borne diseases which are spread by the same mosquito, i.e. the female Aedes aegypti. According to the WHO report, there is a great possibility that humans and mosquitos might be infected by dengue and chikungunya at the same time. Here in this article, a mathematical model approach will be used to understand the spread of dengue and chikungunya in a closed population. A model is developed as a nine-dimensional deterministic ordinary differential equation. Equilibrium points and their local stability are analyzed analytically and numerically. We find that the basic reproduction number, the endemic indicator, is given by the maximum of three different basic reproduction numbers of a complete system, i.e. basic reproduction numbers for dengue, chikungunya and for co-infection between dengue and chikungunya. We find that the basic reproduction number for the co-infection sub-system dominates other basic reproduction numbers whenever it is larger than one. Some numerical simulations are provided to confirm these analytical results.

  8. Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model

    Energy Technology Data Exchange (ETDEWEB)

    Kidwai, Afshan S.; Mushamiri, Ivy T.; Niemann, George; Brown, Roslyn N.; Adkins, Joshua N.; Heffron, Fred

    2013-08-12

    Salmonella enterica serovar Typhimurium causes typhoid-like disease in mice and is a model of typhoid fever in humans. One of the hallmarks of typhoid is persistence, the ability of the bacteria to survive in the host weeks after infection. Virulence factors called effectors facilitate this process by direct transfer to the cytoplasm of infected cells thereby subverting cellular processes. Secretion of effectors to the cell cytoplasm takes place through multiple routes, including two separate type III secretion (T3SS) apparati as well as outer membrane vesicles. The two T3SS are encoded on separate pathogenicity islands, SPI-1 and -2, with SPI-1 more strongly associated with the intestinal phase of infection, and SPI-2 with the systemic phase. Both T3SS are required for persistence, but the effectors required have not been systematically evaluated. In this study, mutations in 48 described effectors were tested for persistence. We replaced each effector with a specific DNA barcode sequence by allelic exchange and co-infected with a wild-type reference to calculate the ratio of wild-type parent to mutant at different times after infection. The competitive index (CI) was determined by quantitative PCR in which primers that correspond to the barcode were used for amplification. Mutations in all but seven effectors reduced persistence demonstrating that most effectors were required. One exception was CigR, a recently discovered effector that is widely conserved throughout enteric bacteria. Deletion of cigR increased lethality, suggesting that it may be an anti-virulence factor. The fact that almost all Salmonella effectors are required for persistence argues against redundant functions. This is different from effector repertoires in other intracellular pathogens such as Legionella.

  9. Diverse secreted effectors are required for Salmonella persistence in a mouse infection model.

    Directory of Open Access Journals (Sweden)

    Afshan S Kidwai

    Full Text Available Salmonella enterica serovar Typhimurium causes typhoid-like disease in mice and is a model of typhoid fever in humans. One of the hallmarks of typhoid is persistence, the ability of the bacteria to survive in the host weeks after infection. Virulence factors called effectors facilitate this process by direct transfer to the cytoplasm of infected cells thereby subverting cellular processes. Secretion of effectors to the cell cytoplasm takes place through multiple routes, including two separate type III secretion (T3SS apparati as well as outer membrane vesicles. The two T3SS are encoded on separate pathogenicity islands, SPI-1 and -2, with SPI-1 more strongly associated with the intestinal phase of infection, and SPI-2 with the systemic phase. Both T3SS are required for persistence, but the effectors required have not been systematically evaluated. In this study, mutations in 48 described effectors were tested for persistence. We replaced each effector with a specific DNA barcode sequence by allelic exchange and co-infected with a wild-type reference to calculate the ratio of wild-type parent to mutant at different times after infection. The competitive index (CI was determined by quantitative PCR in which primers that correspond to the barcode were used for amplification. Mutations in all but seven effectors reduced persistence demonstrating that most effectors were required. One exception was CigR, a recently discovered effector that is widely conserved throughout enteric bacteria. Deletion of cigR increased lethality, suggesting that it may be an anti-virulence factor. The fact that almost all Salmonella effectors are required for persistence argues against redundant functions. This is different from effector repertoires in other intracellular pathogens such as Legionella.

  10. In vivo bioluminescence imaging of Burkholderia mallei respiratory infection and treatment in the mouse model

    Directory of Open Access Journals (Sweden)

    Shane eMassey

    2011-08-01

    Full Text Available Bioluminescent imaging (BLI technology is a powerful tool for monitoring infectious disease progression and treatment approaches. BLI is particularly useful for tracking fastidious intracellular pathogens that might be difficult to recover from certain organs. Burkholderia mallei, the causative agent of glanders, is a facultative intracellular pathogen and has been classified by the CDC as a Category B select agent due to its highly infectious nature and potential use as a biological weapon. Very little is known regarding pathogenesis or treatment of glanders. We investigated the use of bioluminescent reporter constructs to monitor the dynamics of infection as well as the efficacy of therapeutics for B. mallei in real time. A stable luminescent reporter B. mallei strain was created using the pUTmini-Tn5::luxKm2 plasmid and used to monitor glanders in the BALB/c murine model. Mice were infected via the intranasal route with 5x103 bacteria and monitored by BLI at 24, 48 and 72 h. We verified that our reporter construct maintained similar virulence and growth kinetics compared to wild-type B. mallei and confirmed that it maintains luminescent stability in the presence or absence of antibiotic selection. The luminescent signal was initially seen in the lungs, and progressed to the liver and spleen over the course of infection. We demonstrated that antibiotic treatment 24 h post-infection resulted in reduction of bioluminescence that can be attributed to decreased bacterial burden in target organs. These findings suggest that BLI can be used to monitor disease progression and efficacy of therapeutics during glanders infections. Finally, we report an alternative method to mini-Tn5::luxKm2 transposon using mini-Tn7-lux elements that insert site-specifically at known genomic attachment sites and that can also be used to tag bacteria.

  11. Reactivating dynamics for the susceptible-infected-susceptible model: a simple method to simulate the absorbing phase

    Science.gov (United States)

    Macedo-Filho, A.; Alves, G. A.; Costa Filho, R. N.; Alves, T. F. A.

    2018-04-01

    We investigated the susceptible-infected-susceptible model on a square lattice in the presence of a conjugated field based on recently proposed reactivating dynamics. Reactivating dynamics consists of reactivating the infection by adding one infected site, chosen randomly when the infection dies out, avoiding the dynamics being trapped in the absorbing state. We show that the reactivating dynamics can be interpreted as the usual dynamics performed in the presence of an effective conjugated field, named the reactivating field. The reactivating field scales as the inverse of the lattice number of vertices n, which vanishes at the thermodynamic limit and does not affect any scaling properties including ones related to the conjugated field.

  12. The pig as a large animal model for influenza a virus infection

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Brogaard, Louise; Larsen, Lars Erik

    It is increasingly realized that large animal models like the pig are exceptionally human like and serve as an excellent model for disease and inflammation. Pigs are fully susceptible to human influenza, share many similarities with humans regarding lung physiology and innate immune cell infiltra......It is increasingly realized that large animal models like the pig are exceptionally human like and serve as an excellent model for disease and inflammation. Pigs are fully susceptible to human influenza, share many similarities with humans regarding lung physiology and innate immune cell...... of immune factors including several genes known to be centrally involved in the viral defence was quantified by high throughput qPCR (BioMark, Fluidigm). Likewise, miRNAs were quantified using the BioMark (Fluidigm) as well as by MiRCURY LNATM (Exiqon). During the first 24 hours of infection we found...

  13. Dynamics of a delay differential equation model of hepatitis B virus infection.

    Science.gov (United States)

    Gourley, Stephen A; Kuang, Yang; Nagy, John D

    2008-04-01

    We formulate and systematically study the global dynamics of a simple model of hepatitis B virus in terms of delay differential equations. This model has two important and novel features compared to the well-known basic virus model in the literature. Specifically, it makes use of the more realistic standard incidence function and explicitly incorporates a time delay in virus production. As a result, the infection reproduction number is no longer dependent on the patient liver size (number of initial healthy liver cells). For this model, the existence and the component values of the endemic steady state are explicitly dependent on the time delay. In certain biologically interesting limiting scenarios, a globally attractive endemic equilibrium can exist regardless of the time delay length.

  14. Efficacy of voriconazole in a murine model of acute Trypanosoma cruzi infection.

    Science.gov (United States)

    Gulin, J E N; Eagleson, M A; Postan, M; Cutrullis, R A; Freilij, H; Bournissen, F Garcia; Petray, P B; Altcheh, J

    2013-04-01

    Antifungal triazole derivatives have been studied as possible alternatives for the treatment of Chagas' disease. Voriconazole has demonstrated in vitro activity against Trypanosoma cruzi, but its efficacy in vivo has not yet been tested. We aimed to determine the effect of voriconazole in a murine model of acute T. cruzi infection. Treatment efficacy was evaluated by comparing parasitaemia, mortality and organ involvement (by histological examination) of infected mice. Treatment with voriconazole significantly lowered parasitaemia and mortality compared with controls, reduced the percentage of mice with amastigote nests in heart and skeletal muscle and moderately decreased myocardial inflammation. Our findings support the potential of voriconazole for the treatment of acute Chagas' disease and motivate future animal studies using varying doses and treatment schemes. Further evaluation of voriconazole for clinical use in human Chagas' patients is warranted.

  15. Replication of type 5 adenovirus promotes middle ear infection by Streptococcus pneumoniae in the chinchilla model of otitis media.

    Science.gov (United States)

    Murrah, Kyle A; Turner, Roberta L; Pang, Bing; Perez, Antonia C; Reimche, Jennifer L; King, Lauren B; Wren, John; Gandhi, Uma; Swords, W Edward; Ornelles, David A

    2015-03-01

    Adenoviral infection is a major risk factor for otitis media. We hypothesized that adenovirus promotes bacterial ascension into the middle ear through the disruption of normal function in the Eustachian tubes due to inflammation-induced changes. An intranasal infection model of the chinchilla was used to test the ability of type 5 adenovirus to promote middle ear infection by Streptococcus pneumoniae. The hyperinflammatory adenovirus mutant dl327 and the nonreplicating adenovirus mutant H5wt300ΔpTP were used to test the role of inflammation and viral replication, respectively, in promotion of pneumococcal middle ear infection. Precedent infection with adenovirus resulted in a significantly greater incidence of middle ear disease by S. pneumoniae as compared to nonadenovirus infected animals. Infection with the adenovirus mutant dl327 induced a comparable degree of bacterial ascension into the middle ear as did infection with the wild-type virus. By contrast, infection with the nonreplicating adenovirus mutant H5wt300ΔpTP resulted in less extensive middle ear infection compared to the wild-type adenovirus. We conclude that viral replication is necessary for adenoviral-induced pneumococcal middle ear disease. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Replication of type 5 adenovirus promotes middle ear infection by Streptococcus pneumoniae in the chinchilla model of otitis media

    Science.gov (United States)

    Murrah, Kyle A.; Turner, Roberta L.; Pang, Bing; Perez, Antonia C.; Reimche, Jennifer L.; King, Lauren B.; Wren, John; Gandhi, Uma; Swords, W. Edward; Ornelles, David A.

    2015-01-01

    Adenoviral infection is a major risk factor for otitis media. We hypothesized that adenovirus promotes bacterial ascension into the middle ear through the disruption of normal function in the Eustachian tubes due to inflammation-induced changes. An intranasal infection model of the chinchilla was used to test the ability of type 5 adenovirus to promote middle ear infection by Streptococcus pneumoniae. The hyperinflammatory adenovirus mutant dl327 and the nonreplicating adenovirus mutant H5wt300ΔpTP were used to test the role of inflammation and viral replication, respectively, in promotion of pneumococcal middle ear infection. Precedent infection with adenovirus resulted in a significantly greater incidence of middle ear disease by S. pneumoniae as compared to nonadenovirus infected animals. Infection with the adenovirus mutant dl327 induced a comparable degree of bacterial ascension into the middle ear as did infection with the wild-type virus. By contrast, infection with the nonreplicating adenovirus mutant H5wt300ΔpTP resulted in less extensive middle ear infection compared to the wild-type adenovirus. We conclude that viral replication is necessary for adenoviral-induced pneumococcal middle ear disease. PMID:25251686

  17. Strongyloides stercoralis-infected dogs as a model for human disseminated strongyloidiasis

    International Nuclear Information System (INIS)

    Aikens, L.M.

    1989-01-01

    The route of migration of Strongyloides stercoralis third-stage infective larvae was explored in primary and autogenous infections in the dog. Larvae was radiolabeled by one of two means: (1) by culture of the free-living L3 stage in a nutrient medium, deficient in methionine, supplemented with [ 75 Se]Selenomethionine, and (2) by feeding of [ 75 Se]Selenomethionine-labeled bacteria to microbiverous L1 and L2 stages. Third-stage labeled larvae were then injected into 10-day-old pups either subcutaneously, to study primary migration, or into the distal ileum, to study autogenous migration. At intervals after infection pups were killed and whole body compressed organ autoradiography done on individual tissues to determine organ-specific larval transit sites. Autoradiographic recoveries were analyzed in the context of a series of mathematical models designed to test migratory route hypotheses. Postulated routes of migration for primary infections included (1) the Null Hypothesis or Scramble Route in which larvae migrate to the intestines by any available route, (2) the Classical Pulmonary Route in which larvae migrate sequentially from skin, to blood, to lungs, to the trachea, esophagus and intestines, and (3) the Head Migration Route in which larvae move from caudal to cranial sites within the skin and muscle before entering the intestines. Postulated routes for autoinfective migration reiterated 1 and 2 above. Least squares comparisons, of calculated models to observed autoradiographic distributions, led us to conclude that there was no reason to reject the simplest assumption that larvae move by any available route to the definitive site in both forms of migration. Sampling through tracheostomy sites in 14 pups for larval migrants confirmed this conclusion

  18. A Virtual Infection Model Quantifies Innate Effector Mechanisms and Candida albicans Immune Escape in Human Blood

    Science.gov (United States)

    Bieber, Kristin; Martin, Ronny; Figge, Marc Thilo; Kurzai, Oliver

    2014-01-01

    Candida albicans bloodstream infection is increasingly frequent and can result in disseminated candidiasis associated with high mortality rates. To analyze the innate immune response against C. albicans, fungal cells were added to human whole-blood samples. After inoculation, C. albicans started to filament and predominantly associate with neutrophils, whereas only a minority of fungal cells became attached to monocytes. While many parameters of host-pathogen interaction were accessible to direct experimental quantification in the whole-blood infection assay, others were not. To overcome these limitations, we generated a virtual infection model that allowed detailed and quantitative predictions on the dynamics of host-pathogen interaction. Experimental time-resolved data were simulated using a state-based modeling approach combined with the Monte Carlo method of simulated annealing to obtain quantitative predictions on a priori unknown transition rates and to identify the main axis of antifungal immunity. Results clearly demonstrated a predominant role of neutrophils, mediated by phagocytosis and intracellular killing as well as the release of antifungal effector molecules upon activation, resulting in extracellular fungicidal activity. Both mechanisms together account for almost of C. albicans killing, clearly proving that beside being present in larger numbers than other leukocytes, neutrophils functionally dominate the immune response against C. albicans in human blood. A fraction of C. albicans cells escaped phagocytosis and remained extracellular and viable for up to four hours. This immune escape was independent of filamentation and fungal activity and not linked to exhaustion or inactivation of innate immune cells. The occurrence of C. albicans cells being resistant against phagocytosis may account for the high proportion of dissemination in C. albicans bloodstream infection. Taken together, iterative experiment–model–experiment cycles allowed

  19. Heterogeneity in the Infection Biology of Campylobacter jejuni Isolates in Three Infection Models Reveals an Invasive and Virulent Phenotype in a ST21 Isolate from Poultry.

    Directory of Open Access Journals (Sweden)

    Suzanne Humphrey

    Full Text Available Although Campylobacter is the leading cause of bacterial foodborne gastroenteritis in the world and the importance of poultry as a source of infection is well understood we know relatively little about its infection biology in the broiler chicken. Much of what we know about the biology of Campylobacter jejuni is based on infection of inbred or SPF laboratory lines of chickens with a small number of isolates used in most laboratory studies. Recently we have shown that both the host response and microbial ecology of C. jejuni in the broiler chicken varies with both the host-type and significantly between C. jejuni isolates. Here we describe heterogeneity in infection within a panel of C. jejuni isolates in two broiler chicken breeds, human intestinal epithelial cells and the Galleria insect model of virulence. All C. jejuni isolates colonised the chicken caeca, though colonisation of other parts of the gastrointestinal tract varied between isolates. Extra-intestinal spread to the liver varied between isolates and bird breed but a poultry isolate 13126 (sequence type 21 showed the greatest levels of extra-intestinal spread to the liver in both broiler breeds with over 70% of birds of the fast growing breed and 50% of the slower growing breed having C. jejuni in their livers. Crucially 13126 is significantly more invasive than other isolates in human intestinal epithelial cells and gave the highest mortality in the Galleria infection model. Taken together our findings suggest that not only is there considerable heterogeneity in the infection biology of C. jejuni in avian, mammalian and alternative models, but that some isolates have an invasive and virulent phenotype. Isolates with an invasive phenotype would pose a significant risk and increased difficulty in control in chicken production and coupled with the virulent phenotype seen in 13126 could be an increased risk to public health.

  20. Mathematical modeling on T-cell mediated adaptive immunity in primary dengue infections.

    Science.gov (United States)

    Sasmal, Sourav Kumar; Dong, Yueping; Takeuchi, Yasuhiro

    2017-09-21

    At present, dengue is the most common mosquito-borne viral disease in the world, and the global dengue incidence is increasing day by day due to climate changing. Here, we present a mathematical model of dengue viruses (DENVs) dynamics in micro-environment (cellular level) consisting of healthy cells, infected cells, virus particles and T-cell mediated adaptive immunity. We have considered the explicit role of cytokines and antibody in our model. We find that the virus load goes down to zero within 6 days as it is common for DENV infection. From our analysis, we have identified the important model parameters and done the numerical simulation with respect to such important parameters. We have shown that the cytokine mediated virus clearance plays a very important role in dengue dynamics. It can change the dynamical behavior of the system and causes essential extinction of the virus. Finally, we have incorporated the antiviral treatment for dengue in our model and shown that the basic reproduction number is directly proportional to the antiviral treatment effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. A Simple Model to Identify Risk of Sarcopenia and Physical Disability in HIV-Infected Patients.

    Science.gov (United States)

    Farinatti, Paulo; Paes, Lorena; Harris, Elizabeth A; Lopes, Gabriella O; Borges, Juliana P

    2017-09-01

    Farinatti, P, Paes, L, Harris, EA, Lopes, GO, and Borges, JP. A simple model to identify risk of sarcopenia and physical disability in HIV-infected patients. J Strength Cond Res 31(9): 2542-2551, 2017-Early detection of sarcopenia might help preventing muscle loss and disability in HIV-infected patients. This study proposed a model for estimating appendicular skeletal muscle mass (ASM) to calculate indices to identify "sarcopenia" (SA) and "risk for disability due to sarcopenia" (RSA) in patients with HIV. An equation to estimate ASM was developed in 56 patients (47.2 ± 6.9 years), with a cross-validation sample of 24 patients (48.1 ± 6.6 years). The model validity was determined by calculating, in both samples: (a) Concordance between actual vs. estimated ASM; (b) Correlations between actual/estimated ASM vs. peak torque (PT) and total work (TW) during isokinetic knee extension/flexion; (c) Agreement of patients classified with SA and RSA. The predictive equation was ASM (kg) = 7.77 (sex; F = 0/M = 1) + 0.26 (arm circumference; cm) + 0.38 (thigh circumference; cm) + 0.03 (Body Mass Index; kg·m) - 8.94 (R = 0.74; Radj = 0.72; SEE = 3.13 kg). Agreement between actual vs. estimated ASM was confirmed in validation (t = 0.081/p = 0.94; R = 0.86/p ASM were of 87.5% and 77.2% (gamma correlations 0.72-1.0; p ASM vs. PT (range 0.50-0.73, p ≤ 0.05) and TW (range 0.59-0.74, p ≤ 0.05) were similar in both samples. In conclusion, our model correctly estimated ASM to determine indices for identifying SA and RSA in HIV-infected patients.

  2. Innate Immunity of Adipose Tissue in Rodent Models of Local and SystemicStaphylococcus aureusInfection.

    Science.gov (United States)

    Schmid, Andreas; Karrasch, Thomas; Thomalla, Miriam; Schlegel, Jutta; Salzberger, Bernd; Schäffler, Andreas; Hanses, Frank

    2017-01-01

    Background . The role of adipose tissue in systemic inflammation during bacterial infection is unclear. Effects of Staphylococcus aureus infection on adipocytes in rodent models of experimental endocarditis and peritonitis, the impact of S. aureus infection on gene expression in epididymal and subcutaneous adipose tissue, and effects of S. aureus infection on the toll-like receptor-2- (TLR2-) cathelicidin pathway in vivo and in vitro were investigated. Material and methods. The rat model of catheter-induced S. aureus endocarditis and the mouse model of S. aureus -induced peritonitis were used for infection experiments, gene expression profiling in adipose tissue, and measurement of cytokines. 3T3-L1 adipocytes were analyzed for expression of the TLR2-cathelicidin pathway. Results . Upon systemic bacterial infection by S. aureus , there is a shift from anti- to proinflammatory cytokines in serum and in adipose tissue gene expression. The TLR2-cathelicidin pathway is increasingly expressed during adipocyte differentiation in vitro and is induced upon stimulation by synthetic lipopeptides. Conclusions . Systemic infection by Gram-positive bacteria induces proinflammatory transformation of adipose tissue sites distinct from infection sites, documented on the levels of gene expression and secreted mediators. The TLR2-cathelicidine pathway is expressed and highly inducible in adipocytes in vitro. Lipopeptides are important immune-modulators of adipocytes in both gene expression and protein secretion.

  3. Immunogenic multistage recombinant protein vaccine confers partial protection against experimental toxoplasmosis mimicking natural infection in murine model

    Directory of Open Access Journals (Sweden)

    Yaprak Gedik

    2016-01-01

    To generate a protective vaccine against toxoplasmosis, multistage vaccines and usage of challenging models mimicking natural route of infection are critical cornerstones. In this study, we generated a BAG1 and GRA1 multistage vaccine that induced strong immune response in which the protection was not at anticipated level. In addition, the murine model was orally challenged with tissue cysts to mimic natural route of infection.

  4. Asymptotic behavior and numerical simulations for an infection load-structured epidemiological model; Application to the transmission of prion pathologies

    OpenAIRE

    Perasso, Antoine; Razafison, Ulrich

    2014-01-01

    In this article is studied an infection load-structured SI model with exponential growth of the infection, that incorporates a potential external source of contamination. We perform the analysis of the time asymptotic behavior of the solution by exhibiting epidemiological thresholds, such as the basic reproduction number, that ensure extinction or persistence of the disease in the contagion process. Moreover, a numerical scheme adapted to the model is developped and analyzed. This scheme is t...

  5. Comparative therapeutic activities of Ciprofloxacin, Amoxicillin, Ceftriaxone and Cotrimoxazole in a new model of experimental infection with Escherichia coli

    OpenAIRE

    Hof, H.; Christen, A.; Hacker, Jörg

    2009-01-01

    A new mouse model for systemic infection with Escherichia coli is presented. Whereas in other models 107_108 bacteria have to be injected into an animal to induce toxic effects resulting in death within 24 hours, now, only 103_104 bacteria of an appropriate strain are required to produce a genuine infection characterized by an increase in the bacterial load over several days. The quantitative determination of bacterial counts per liver allows a more sensitive measurement than recording death ...

  6. Comparability of results from pair and classical model formulations for different sexually transmitted infections.

    Directory of Open Access Journals (Sweden)

    Jimmy Boon Som Ong

    Full Text Available The "classical model" for sexually transmitted infections treats partnerships as instantaneous events summarized by partner change rates, while individual-based and pair models explicitly account for time within partnerships and gaps between partnerships. We compared predictions from the classical and pair models over a range of partnership and gap combinations. While the former predicted similar or marginally higher prevalence at the shortest partnership lengths, the latter predicted self-sustaining transmission for gonorrhoea (GC and Chlamydia (CT over much broader partnership and gap combinations. Predictions on the critical level of condom use (C(c required to prevent transmission also differed substantially when using the same parameters. When calibrated to give the same disease prevalence as the pair model by adjusting the infectious duration for GC and CT, and by adjusting transmission probabilities for HIV, the classical