Cutaneous Infection by Different Alternaria Species in a Liver Transplant Recipient

Fungal invasive infections are rare in general population but are an emergent cause of infection in the immunocompromized population, especially in the solid organ transplant recipients. Herein the authors report a clinical case of a liver transplanted patient suffering a cutaneous co-existent infection with A. alternata as well as A. infectoria. To our knowledge this is the first case of cutaneous concomitant infection due to those two species reported not only in Portugal but also worldwide. The patient was treated with surgical excision of the lesions and oral itraconazol without relapse.

Natural cutaneous anthrax infection, but not vaccination, induces a CD4+ T cell response involving diverse cytokines

Background

Whilst there have been a number of insights into the subsets of CD4⁺ T cells induced by pathogenicBacillus anthracis infections in animal models, how these findings relate to responses generated in naturally infected and vaccinated humans has yet to be fully established. We describe the cytokine profile produced in response to T cell stimulation with a previously defined immunodominant antigen of anthrax, lethal factor (LF), domain IV, in cohorts of individuals with a history of cutaneous anthrax, compared with vaccinees receiving the U.K. licenced Anthrax Vaccine Precipitated (AVP) vaccine.

We found that immunity following natural cutaneous infection was significantly different from that seen after vaccination. AVP vaccination was found to result in a polarized IFNγ CD4+ T cell response, while the individuals exposed to B. anthracis by natural infection mounted a broader cytokine response encompassing IFNγ, IL-5, −9, −10, −13, −17, and −22.

Vaccines seeking to incorporate the robust, long-lasting, CD4 T cell immune responses observed in naturally acquired cutaneous anthrax cases may need to elicit a similarly broad spectrum cellular immune response.

Langerhans cells promote early germinal center formation in response to Leishmania-derived cutaneous antigens

Efficient formation of early GCs depends on the close interaction between GC B cells and antigen-primed CD4+ follicular helper T cells (TFH). A tight and stable formation of TFH/B cell conjugates is required for cytokine-driven immunoglobulin class switching and somatic hypermutation of GC B cells. Recently, it has been shown that the formation of TFH/B cell conjugates is crucial for B-cell differentiation and class switch following infection with Leishmania major parasites. However, the subtype of DCs responsible for TFH-cell priming against dermal antigens is thus far unknown. Utilizing a transgenic C57BL/6 mouse model designed to trigger the ablation of Langerin+ DC subsets in vivo, we show that the functionality of TFH/B cell conjugates is disturbed after depletion of Langerhans cells (LCs): LC-depleted mice show a reduction in somatic hypermutation in B cells isolated from TFH/B cell conjugates and markedly reduced GC reactions within skin-draining lymph nodes. In conclusion, this study reveals an indispensable role for LCs in promoting GC B-cell differentiation following cutaneous infection with Leishmania major parasites. We propose that LCs are key regulators of GC formation and therefore have broader implications for the development of allergies and autoimmunity as well as for future vaccination strategies.

Whole genome protein microarrays for serum profiling of immunodominant antigens of Bacillus anthracis

A commercial Bacillus anthracis (Anthrax) whole genome protein microarray has been used to identify immunogenic Anthrax proteins (IAP) using sera from groups of donors with (a) confirmed B. anthracis naturally acquired cutaneous infection, (b) confirmed B. anthracis intravenous drug use-acquired infection, (c) occupational exposure in a wool-sorters factory, (d) humans and rabbits vaccinated with the UK Anthrax protein vaccine and compared to naïve unexposed controls. Anti-IAP responses were observed for both IgG and IgA in the challenged groups; however the anti-IAP IgG response was more evident in the vaccinated group and the anti-IAP IgA response more evident in the B. anthracis-infected groups. Infected individuals appeared somewhat suppressed for their general IgG response, compared with other challenged groups. Immunogenic protein antigens were identified in all groups, some of which were shared between groups whilst others were specific for individual groups. The toxin proteins were immunodominant in all vaccinated, infected or other challenged groups. However, a number of other chromosomally-located and plasmid encoded open reading frame proteins were also recognized by infected or exposed groups in comparison to controls. Some of these antigens e.g., BA4182 are not recognized by vaccinated individuals, suggesting that there are proteins more specifically expressed by live Anthrax spores in vivo that are not currently found in the UK licensed Anthrax Vaccine (AVP). These may perhaps be preferentially expressed during infection and represent expression of alternative pathways in the B. anthracis "infectome." These may make highly attractive candidates for diagnostic and vaccine biomarker development as they may be more specifically associated with the infectious phase of the pathogen. A number of B. anthracis small hypothetical protein targets have been synthesized, tested in mouse immunogenicity studies and validated in parallel using human sera from the same study.

Cladophialophora saturnica sp nov., a new opportunistic species of Chaetothyriales revealed using molecular data

While many members of the black yeasts genus Cladophialophora have been reported to cause diseases in humans, understanding of their natural niche is frequently lacking. Some species can be recovered from the natural environment by means of selective isolation techniques. The present study focuses on a Cladophialophora strain that caused an interdigital tinea nigra-like lesion in a HIV-positive Brazilian child. The fungal infection was successfully treated with oxiconazole. Similar strains had been recovered from the environment in Brazil, Uruguay and the Netherlands. The strains were characterized by sequencing the Internal Transcribed Spacer (ITS) regions and the small subunit (SSU) of the nuclear ribosomal RNA gene, as well as the elongation factor 1-alpha (EF1) gene. Since no match with any known species was found, it is described as the new species, Cladophialophora saturnica.

Aspecto sanitário de pisciculturas do litoral sul catarinense

Pós-graduação em Medicina Veterinária - FCAV

Sodium fluorescein for early detection of skin ulcers in Aeromonas hydrophila infected Piaractus mesopotamicus

The increase in aquaculture global fish production has been associated with an increase in infectious diseases affecting aquacultured species.. The aim of this study was to identify ulcers in pacu (Piaractus mesopotamicus) with sodium fluorescein before it was possible to observe them visually. Twenty one fish with no apparent skin lesions were divided into three groups. Group 1 were injected with saline 0.65% (Group 1), Group 2 with 6 x 10(8) CFU of Aeromonas hydrophila and group 3 with 6 x 10(8) CFU of Streptococcus agalactiae into the peritoneal cavity. All animals showed a positive reaction to fluorescein. A. hydrophila infected fish presented with large round marks with irregular borders, the characteristic ulcers caused by this agent. However, the other groups only displayed markings associated with handling caused by the netting procedures. We concluded that sodium fluorescein may be useful for an early and fast evaluation of cutaneous infection of A. hydrophila in pacu.

Markers of cutaneous human papillomavirus infection in individuals with tumor-free skin, actinic keratoses, and squamous cell carcinoma

Separately, actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) have been associated with cutaneous human papillomavirus (HPV) infections. To further explore the association between HPV infection and SCC development, we determined markers of cutaneous HPV infection within a single population in persons with precursor lesions (AK), cancerous lesions (SCC), and without. Serum and plucked eyebrow hairs were collected from 57 tumor-free controls, 126 AK, and 64 SCC cases. Presence of HPV L1 and E6 seroreactivity and viral DNA were determined for HPV types 5, 8, 15, 16, 20, 24, and 38. Significant positive associations with increasing severity of the lesions (controls, AK, and SCC, respectively) were observed for overall HPV L1 seropositivity (13%, 26%, and 37%) and for HPV8 (4%, 17%, and 30%). In parallel, the proportion of L1 seropositive individuals against multiple HPV types increased from 14% to 39% and 45%. The overall E6 seroreactivity, however, tended to decline with AK and SCC, especially for HPV8 (21%, 11%, and 2%). HPV DNA positivity was most prevalent in the AK cases (54%) compared with the SCC cases (44%) and the tumor-free controls (40%). Among all participants, there was a positive trend between overall HPV DNA positivity and L1 seropositivity, but not E6 seropositivity. Taken together, our data suggest that cutaneous HPV infections accompanied by detectable HPV DNA in eyebrow hairs and HPV L1 seropositivity, but not E6 seropositivity, are associated with an increased risk of AK and SCC.

Natural Exposure to Cutaneous Anthrax Gives Long-Lasting T Cell Immunity Encompassing Infection-Specific Epitopes

There has been a long history of defining T cell epitopes to track viral immunity and to design rational vaccines, yet few data of this type exist for bacterial infections. Bacillus anthracis, the causative agent of anthrax, is both an endemic pathogen in many regions and a potential biological warfare threat. T cell immunity in naturally infected anthrax patients has not previously been characterized, which is surprising given concern about the ability of anthrax toxins to subvert or ablate adaptive immunity. We investigated CD4 T cell responses in patients from the Kayseri region of Turkey who were previously infected with cutaneous anthrax. Responses to B. anthracis protective Ag and lethal factor (LF) were investigated at the protein, domain, and epitope level. Several years after antibiotic-treated anthrax infection, strong T cell memory was detectable, with no evidence of the expected impairment in specific immunity. Although serological responses to existing anthrax vaccines focus primarily on protective Ag, the major target of T cell immunity in infected individuals and anthrax-vaccinated donors was LF, notably domain IV. Some of these anthrax epitopes showed broad binding to several HLA class alleles, but others were more constrained in their HLA binding patterns. Of specific CD4 T cell epitopes targeted within LF domain IV, one is preferentially seen in the context of bacterial infection, as opposed to vaccination, suggesting that studies of this type will be important in understanding how the human immune system confronts serious bacterial infection.

Disseminated Mycobacterium marinum infection with extensive cutaneous eruption and bacteremia in an immunocompromised patient

Mycobacterium marinum can cause fish tank granuloma (or swimming pool or aquarium granuloma) in immunocompetent patients. Dissemination of Mycobacterium marinum-infection is a rare condition which occurs mainly in immunocompromised patients and can be life-threatening. We report the case of an 87-year-old woman who was treated with oral corticosteroids for polymyalgia rheumatica for many years and developed erythema nodosum-like lesions on the right forearm and arthritis of the right wrist. By increasing the steroid dosage and adding methotrexate only short-term remission was achieved. Seven months later painful erythematous nodules occurred on all extremities which became necrotic, ulcerative and suppurative. Ziehl-Neelsen staining revealed acid-fast bacilli and Mycobacterium marinum was cultured from skin biopsies, blood, and urine. The critically ill patient was treated with clarithromycin and ethambutol resulting in a dramatic improvement of the general condition. After four months, doxycycline had to be added because of new skin lesions. This case illustrates the impact of Mycobacterium marinum infection in immunocompromised patients.

Cutaneous lesions associated with dual infection caused by canine distemper virus and orthopoxvirus in a domestic cat.

BACKGROUND Within the context of an increased epidemiological pressure caused by canine distemper virus (CDV) in Switzerland together with a potential re-emergence of endemic pathogens such as orthopoxviruses (OPXV), dual infections are possible among susceptible species. OBJECTIVE To describe a case of concurrent CDV and OPXV infection in a cat. ANIMAL A 5-year-old, neutered male cat was presented with erythema, crusts and ulcerations around the left eye. High-grade pruritus and a severe conjunctivitis were also present. METHODS Formalin-fixed skin biopsy samples were obtained from lesional skin. Histopathology, CDV immunohistochemistry and CDV and OPXV RT-PCR were performed. RESULTS Histopathological examination showed severe epidermal necrosis extending to the follicular walls and a dermal infiltration, predominantly eosinophilic. Intranuclear and intracytoplasmic eosinophilic inclusion bodies were visible in the wall of affected hair follicles, with occasional formation of syncytia. The RT-PCR revealed the contextual presence of both CDV and OPXV. Scattered cells stained positive for CDV by immunohistochemistry. CONCLUSION AND DISCUSSION Dual infections with CDV and OPXV, although rare, may occur and represent additional differential diagnoses for ulcerative skin lesions in cats.

Silver deposits in cutaneous burn scar tissue is a common phenomenon following application of a silver dressing

BACKGROUND Silver dressings have been widely and successfully used to prevent cutaneous wounds, including burns, chronic ulcers, dermatitis and other cutaneous conditions, from infection. However, in a few cases, skin discolouration or argyria-like appearances have been reported. This study investigated the level of silver in scar tissue post-burn injury following application of Acticoat, a silver dressing. METHODS A porcine deep dermal partial thickness burn model was used. Burn wounds were treated with this silver dressing until completion of re-epithelialization, and silver levels were measured in a total of 160 scars and normal tissues. RESULTS The mean level of silver in scar tissue covered with silver dressings was 136 microg/g, while the silver level in normal skin was less than 0.747 microg/g. A number of wounds had a slate-grey appearance, and dissection of the scars revealed brown-black pigment mostly in the middle and deep dermis within the scar. The level of silver and the severity of the slate-grey discolouration were correlated with the length of time of the silver dressing application. CONCLUSIONS These results show that silver deposition in cutaneous scar tissue is a common phenomenon, and higher levels of silver deposits and severe skin discolouration are correlated with an increase in the duration of this silver dressing application.

The role of inflammation in cutaneous repair

Inflammation is a fundamental component of the normal adult wound healing response occurring even in the absence of infection. It performs many beneficial roles such as the clearing of damaged cells and extracellular matrix (ECM), the removal of pathogens that might other wise multiply and spread, and the secretion of mediators that regulate other aspects of wound healing such as proliferation, re-epithelialisation and wound remodelling. Yet, excess and/or prolonged inflammation is detrimental to wound healing and leads to increased fibrosis and scarring, which can be disfiguring and, in cases such as contractures, can lead to disability. Furthermore, excessive inflammation is a major contributing factor to the persistence of chronic non-healing wounds, which are “stuck” in the inflammatory phase of healing and fail to reepithelialise. Current research suggest that the type of immune cells, their timing and the level of inflammation in a wound could have dramatic effect on whether a wound heals in a timely fashion and the final quality of the repaired tissue. Studies suggest that altering the level of inflammation might be beneficial in terms of reducing scarring and improving the rate of healing in chronic wounds. This review looks at the role of the major immune cells in normal and impaired wound healing and strategies that might be used to reduce inflammation in wounds.

A study of HPV 1, 2 and 4 antibody prevalence in patients presenting for treatment with cutaneous warts to general practitioners in N. Ireland

Three hundred and seventy-six patients attending their general practitioner with cutaneous warts at five health centres in Northern Ireland were screened for human papilloma virus (HPV) types 1 and 2 IgM antibody using an indirect immunofluorescence test. Eight-eight (23.4%) patients were positive for HPV type 1 IgM and 156 (41.5%) for HPV type 2 IgM. HPV 1 IgM antibody was significantly more likely to be associated with plantar warts than warts elsewhere (P less than 0.0001). HPV 2 IgM was present in 45 (34.1%) patients with plantar warts and 99 (45.6%) patients with warts at other sites (P = 0.1). Evidence of multiple infection by HPV types 1 and 2 was demonstrated by the finding of HPV 1 and 2 IgM antibodies in the sera of 16 (4.3%). HPV 4 was found in only 1 out of 30 biopsies and HPV 4 IgM was undetectable in 50 randomly chosen sera.