Oral Transmission of Chagas Disease

Chagas disease is now an active disease in the urban centers of countries of nonendemicity and endemicity because of congenital and blood and/or organ transplantation transmissions and the reactivation of the chronic disease in smaller scale than vectorial transmission, reported as controlled in countries of endemicity. Oral transmission of Chagas disease has emerged in unpredictable situations in the Amazon region and, more rarely, in areas of nonendemicity where the domiciliary triatomine cycle was under control because of exposition of the food to infected triatomine and contaminated secretions of reservoir hosts. Oral transmission of Chagas disease is considered when >1 acute case of febrile disease without other causes is linked to a suspected food and should be confirmed by the presence of the parasite after direct microscopic examination of the blood or other biological fluid sample from the patient.

The effects of ultraviolet B radiation on immune responses to {\it Borrelia burgdorferi}, the causative agent of Lyme disease

Ultraviolet B (UVB) radiation, in addition to being carcinogenic, is also immunosuppressive. Immunologically, UVB induces suppression locally, at the site of irradiation, or systemically, by inducing the production of a variety of immunosuppressive cytokines. Systemic effects include suppression of delayed-type hypersensitivity (DTH) responses to a variety of antigens (e.g. haptens, proteins, bacterial antigens, or alloantigens). One of the principal mediators of UV-induced immune suppression is the T helper-2 (Th2) cytokine interleukin-10 (IL-10); this suggests that UV irradiation induces suppression by shifting the immune response from a Th1 (cellular) to a Th2 (humoral) response. These "opposing" T helper responses are usually mutually exclusive, and polarized Th1 or Th2 responses may lead to either protection from infection or increased susceptibility to disease, depending on the infectious agent and the route of infection.^ This study examines the effects of UVB irradiation on cellular and humoral responses to Borrelia burgdorferi (Bb), the causative agent of Lyme disease (LD) in both immunization and infectious disease models; in addition, it examines the role of T cells in protection from and pathology of Bb infection. Particular emphasis is placed on the Bb-specific antibody responses following irradiation since UVB effects on humoral immunity are not fully understood. Mice were irradiated with a single dose of UV and then immunized (in complete Freund's adjuvant) or infected with Bb (intradermally at the base of the tail) in order to examine both DTH and antibody responses in both systems. UVB suppressed the Th1-associated antibodies IgG2a and IgG2b in both systems, as well as the DTH response to Bb in a dose dependent manner. Injection of anti-IL-10 antibody into UV-irradiated mice within 24 h after UV exposure restored the DTH response, as well as the Th1 antibody (IgG2a and IgG2b) response. In addition, injecting recombinant IL-10 mimicked some of the effects of UV radiation.^ Bb-specific Th1 T cell lines (BAT2.1-2.3) were generated to examine the role of T cells in Lyme borreliosis. All lines were CD4$\sp+,$ $\alpha\beta\sp+$ and proliferated specifically in response to Bb. The BAT2 cell lines not only conferred a DTH response to naive C3H recipients, but reduced the number of organisms recovered from the blood and tissues of mice infected with Bb. Furthermore, BAT2 cell lines protected mice from Bb-induced periarthritis. ^

IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE

IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE Publication No.___________ Lisa Harn-Ging Shiue, B.S. Supervisory Professor: Madeleine Duvic, M.D. Extracorporeal photopheresis (ECP) is an effective, low-risk immunomodulating therapy for leukemic cutaneous T cell lymphoma (L-CTCL) and graft versus host disease (GVHD), but whether the mechanism(s) of action in these two diseases is (are) identical or different is unclear. To determine the effects of ECP in vivo, we studied regulatory T cells (T-regs), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs) by immunofluorescence flow cytometry in 18 L-CTCL and 11 GVHD patients before and after ECP at Day 2, 1 month, 3 months, and 6 months. In this study, ECP was effective in 12/18 L-CTCL patients with a 66.7% overall response rate (ORR) and 6/11 GVHD patients with a 54.5% ORR. Prior to ECP, the percentages of CD4+Foxp3+ T cells in 9 L-CTCL patients were either lower (L-CTCL-Low, n=2) or higher (L-CTCL-High, n=7) than normal. Five of the 7 GVHD patients had high percentages of CD4+Foxp3+ T cells (GVHD-High). Six of 7 L-CTCL-High patients had >80% CD4+Foxp3+ T cells which were correlated with tumor cells, and were responders. Both L-CTCL-High and GVHD-High patients had decreased percentages of CD4+Foxp3+ and CD4+Foxp3+CD25- T cells after 3 months of treatment. CD4+Foxp3+CD25+ T cells increased in GVHD-High patients but decreased in L-CTCL-High patients after 3 months of ECP. In addition, numbers of CTLs were abnormal. We confirmed that numbers of CTLs were low in L-CTCL patients, but high in GVHD patients prior to ECP. After ECP, CTLs increased after 1 month in 4/6 L-CTCL patients whereas CTLs decreased after 6 months in 3/3 GVHD patients. Myeloid (mDCs) and plasmacytoid DCs (pDCs) were also low at baseline in L-CTCL and GVHD patients confirming the DC defect. After 6 months of ECP, numbers and percentages of mDCs and pDCs increased in L-CTCL and GVHD. MDCs were favorably increased in 8/12 L-CTCL responders whereas pDCs were favorably increased in GVHD patients. These data suggest that ECP is favorably modulating the DC subsets. In L-CTCL patients, the mDCs may orchestrate Th1 cell responses to overcome immune suppression and facilitate disease regression. However, in GVHD patients, ECP is favorably down-regulating the immune system and may be facilitating immune tolerance to auto-or allo-antigens. In both L-CTCL and GVHD patients, DCs are modulated, but the T cell responses orchestrated by the DCs are different, suggesting that ECP modulates depending on the immune milieu. _______________

Density-dependent decline of host abundance resulting from a new infectious disease

Although many new diseases have emerged within the past 2 decades [Cohen, M. L. (1998) Brit. Med. Bull. 54, 523–532], attributing low numbers of animal hosts to the existence of even a new pathogen is problematic. This is because very rarely does one have data on host abundance before and after the epizootic as well as detailed descriptions of pathogen prevalence [Dobson, A. P. & Hudson, P. J. (1985) in Ecology of Infectious Diseases in Natural Populations, eds. Grenfell, B. T. & Dobson, A. P. (Cambridge Univ. Press, Cambridge, U.K.), pp. 52–89]. Month by month we tracked the spread of the epizootic of an apparently novel strain of a widespread poultry pathogen, Mycoplasma gallisepticum, through a previously unknown host, the house finch, whose abundance has been monitored over past decades. Here we are able to demonstrate a causal relationship between high disease prevalence and declining house finch abundance throughout the eastern half of North America because the epizootic reached different parts of the house finch range at different times. Three years after the epizootic arrived, house finch abundance stabilized at similar levels, although house finch abundance had been high and stable in some areas but low and rapidly increasing in others. This result, not previously documented in wild populations, is as expected from theory if transmission of the disease was density dependent.

Climate and infectious disease: Use of remote sensing for detection of Vibrio cholerae by indirect measurement

It has long been known that cholera outbreaks can be initiated when Vibrio cholerae, the bacterium that causes cholera, is present in drinking water in sufficient numbers to constitute an infective dose, if ingested by humans. Outbreaks associated with drinking or bathing in unpurified river or brackish water may directly or indirectly depend on such conditions as water temperature, nutrient concentration, and plankton production that may be favorable for growth and reproduction of the bacterium. Although these environmental parameters have routinely been measured by using water samples collected aboard research ships, the available data sets are sparse and infrequent. Furthermore, shipboard data acquisition is both expensive and time-consuming. Interpolation to regional scales can also be problematic. Although the bacterium, V. cholerae, cannot be sensed directly, remotely sensed data can be used to infer its presence. In the study reported here, satellite data were used to monitor the timing and spread of cholera. Public domain remote sensing data for the Bay of Bengal were compared directly with cholera case data collected in Bangladesh from 1992–1995. The remote sensing data included sea surface temperature and sea surface height. It was discovered that sea surface temperature shows an annual cycle similar to the cholera case data. Sea surface height may be an indicator of incursion of plankton-laden water inland, e.g., tidal rivers, because it was also found to be correlated with cholera outbreaks. The extensive studies accomplished during the past 25 years, confirming the hypothesis that V. cholerae is autochthonous to the aquatic environment and is a commensal of zooplankton, i.e., copepods, when combined with the findings of the satellite data analyses, provide strong evidence that cholera epidemics are climate-linked.

Study of infectious haematopoietic necrosis disease in some hatcheries and farmed rainbow trout in Iran using immunohistochemical technique and to comparing the obtained results with the PCR works

To detect rainbow trout hatcheries for infectious hematopoietic necrosis virus, samples of kidney, liver, spleen, muscle, intestine, heart and gills of trout larvae were obtained from a number of trout hatcheries from different provinces. Also tissue samples were obtained for molecular works using RT- PCR procedure. Tissue samples were processed using standard histotechnique and the obtained sections were stained using immunohistochemical procedure. From 100 examined samples 35 were positive for IHN by immunohistochemical test. Also, from 100 samples examined, 43 were positive in RT- PCR studies. The obtained results show that some rainbow trout hatcheries are contaminated in different regions of country. Therefore, a definition of prevention and eradication criteria are now critical to protect the unaffected areas within the country.

Wildlife infectious disease dynamics in the context of seasonality and bird migration

The thesis contains chapters that elucidate questions with regards to wildlife infectious disease dynamics - avian influenza in particular - and how those dynamics are affected by seasonality and avian migration.

Geographic variation in seasonality and its influence on the dynamics of an infectious disease

Seasonal changes in environmental drivers - such as temperature, rainfall, and resource availability - have the potential to shape infection dynamics through their reverberating effects on biological processes including host abundance and susceptibility to infection. However, seasonality varies geographically. We therefore expect marked differences in infection dynamics between regions with different seasonal patterns. By pairing extensive Avian Influenza Virus (AIV) surveillance data - 65 358 individual bird samples from 12 species of dabbling ducks sampled at 174 locations across North America - with quantification of seasonality using remote sensed data indicative for primary productivity (normalised differenced vegetation index, NDVI), we provide evidence that seasonal dynamics influence infection dynamics across a continent. More pronounced epidemics were seen to occur in regions experiencing a higher degree of seasonality, and epidemics of lower amplitude and longer duration occurred in regions with a more protracted and lower seasonal amplitude. These results demonstrate the potential importance of geographic variation in seasonality for explaining geographic variation in the dynamics of infectious diseases in wildlife.

Editorial : infectious disease modelling

The aim of this Special Issue is to collect together a group of outstanding applied mathematics research articles that provide new insight into our understanding of infectious diseases and infectious disease modelling. The scope of the articles is broad, encompassing both specific applications of modelling to particular examples of infectious diseases, as well as articles that are devoted to the development of more general theoretical insight.

The mouse model of Chlamydia genital tract infection: a review of infection, disease, immunity and vaccine development

Chlamydia trachomatis is the most common sexually transmitted bacterial infection worldwide. The impact of this pathogen on human reproduction has intensified research efforts to better understand chlamydial infection and pathogenesis. Whilst there are animal models available that mimic the many aspects of human chlamydial infection, the mouse is regarded as the most practical and widely used of the models. Studies in mice have greatly contributed to our understanding of the host-pathogen interaction and provided an excellent medium for evaluating vaccines. Here we explore the advantages and disadvantages of all animal models of chlamydial genital tract infection, with a focus on the murine model and what we have learnt from it so far.

Using internet search queries for infectious disease surveillance: screening diseases for suitability

Background Internet-based surveillance systems provide a novel approach to monitoring infectious diseases. Surveillance systems built on internet data are economically, logistically and epidemiologically appealing and have shown significant promise. The potential for these systems has increased with increased internet availability and shifts in health-related information seeking behaviour. This approach to monitoring infectious diseases has, however, only been applied to single or small groups of select diseases. This study aims to systematically investigate the potential for developing surveillance and early warning systems using internet search data, for a wide range of infectious diseases. Methods Official notifications for 64 infectious diseases in Australia were downloaded and correlated with frequencies for 164 internet search terms for the period 2009–13 using Spearman’s rank correlations. Time series cross correlations were performed to assess the potential for search terms to be used in construction of early warning systems. Results Notifications for 17 infectious diseases (26.6%) were found to be significantly correlated with a selected search term. The use of internet metrics as a means of surveillance has not previously been described for 12 (70.6%) of these diseases. The majority of diseases identified were vaccine-preventable, vector-borne or sexually transmissible; cross correlations, however, indicated that vector-borne and vaccine preventable diseases are best suited for development of early warning systems. Conclusions The findings of this study suggest that internet-based surveillance systems have broader applicability to monitoring infectious diseases than has previously been recognised. Furthermore, internet-based surveillance systems have a potential role in forecasting emerging infectious disease events, especially for vaccine-preventable and vector-borne diseases