Chronic Course Of Infection Research Articles

Клинический случай атипичного течения инфекции Clostridium difficile в сочетании с энтеробиозом у мальчика 14 лет

Clostridium difficile infection is currently a serious medical and epidemiological problem due to a significant and steady increase in the incidence of this pathology. An important causal factor in the increased incidence of Clostridium difficile infection is a widespread and often uncontrolled use of antibiotic therapy. The difficulty in diagnosing Clostridium difficile lies in a wide range of clinical manifestations of this infection, from mild diarrhea to pseudomembranous colitis, toxic megacolon, colon perforation, and multiple organ failure, resulting in a high mortality rate and prolonged length of stay in intensive care units. This article presents a clinical case of Clostridium difficile-associated infection in a 14-year-old boy. An important diagnostic feature of this case is the chronic course of infection, the clinical picture being dominated by pain, hyperthermia, and intoxication without diarrhea, as well as the presence of enterobiasis. This clinical example shows that Clostridium difficile-associated infection does not always present with diarrhea. The etiology of the disease in this case was confirmed not only by the detection of specific Clostridium difficile toxins in the patient’s stool samples, but also by clear positive dynamics with the administration of etiotropic therapy. This article describes the stages of differential diagnostic search and the choice of treatment tactics for Clostridium difficile infection. Key words: clostridium infection, children

A comparative study on susceptibility, course of parasitemia, and pattern of infection with Trypanosoma evansi between different laboratory animals

This study investigated the susceptibility of eight different animal species (rat, mice, guinea pigs, hamsters, rabbits, sheep, goats, and chicken) experimentally infected with Trypanosoma evansi isolated from camels. In all laboratory animals, the number of trypanosomes was standardized according to the weight of the animal, and daily examination of the blood was conducted to assess the presence of trypanosomes to determine the prepatent period and the peak of parasitemia. Results suggested that mice and rats were the most susceptible laboratory animals to infection, whereas hamsters and guinea pigs displayed a certain degree of tolerance to infection. Rabbits exhibited a chronic course of infection, but the level of parasitemia was very low. In sheep and goats, trypanosomes were detectable only by subpassage to rats and mice, whereas all the chickens remained uninfected even with increasing doses of infection.

HIV-INFECTION AND PROBLEMS OF ANTIRETROVIRAL THERAPY EFFECTIVENESS

General data on HIV-infection pathogenesis are presented. Massive destruction of CD4+ T-lymphocytes in the intestine during the acute phase of the disease causes microbial translocation and immune system activation. With a chronic course of infection, persistent immune activation gradually depletes the CD4+ T-lymphocyte pool. Together with AIDS-associated diseases it leads to a fatal outcome against the backdrop of developing immunodeficiency. Efficiency criteria of antiretroviral therapy are also considered. Particular attention is paid to the phenomenon of discordant response to the treatment.

Rare Atypical Presentations in Type 2 Lepra Reaction: A Case Series

BackgroundLeprosy or Hansen’s disease is a chronic mycobacterial infection caused by mycobacterium leprae. Reactions in Leprosy represent an acute inflammataory response during the natural chronic course of infection. Type 2 lepra reaction is a Th2-mediated type III hypersensitivity reaction in leprosy, with a characteristic cutaneous manifestation in the form of erythema nodosum leprosum (ENL). This presentation describes unusual presentations of Type 2 lepra reaction in five patients.MethodsPatient data and dermatological findings were analyzed in three men and two women diagnosed with Hansen’s disease (Leprosy).ResultsFindings included multiple tender, polycyclic, necrotic lesions distributed over the face in one patient, and painful, fluid-filled lesions on both arms and lower limbs in another. The third patient showed erythematous, tender nodules, bullae, and necrotic ulcers over the back and upper and lower limbs. The fourth showed erythematous tender nodules over the face, neck, back, and extremities, predominantly in sun-exposed areas. The fifth revealed multiple erythematous, severely tender nodules and urticarial plaques mimicking those of Sweet’s syndrome. Diagnosis of borderline or lepromatous leprosy with atypical Type 2 reaction were made in all cases.ConclusionType 2 lepra reactions are antigen antibody-mediated immune complex reactions that present with constitutional symptoms and ENL characterized by tender, erythematous, evanescent nodules mainly on the face, arms, and legs. Over 50% of lepromatous leprosy patients and 25% of borderline lepromatous leprosy patients experienced type 2 lepra reactions prior to the advent of multi-drug therapy. Thalidomide is the drug of choice for severe atypical lepra reactions because of its anti-tumor necrosis factor-α action. Awareness of these atypical variants and prompt diagnosis and treatment are essential to prevent mortality and morbidity in potentially treatable patients.Disclosures All authors: No reported disclosures.

Vaccinations for immunocompromised hosts – focussing on patients after a hematological stem cell or organ transplantation, with HIV or with functional or anatomical asplenia

Patients with an acquired immune deficiency, for example due to HIV-infection, after a solid organ or haematological stem cell transplantation or due to functional or anatomical asplenia, have a greater risk to experience severe complications or a chronic course of infection compared to healthy individuals. Vaccinations would pose an ideal primary preventive method. However, their efficacy is reduced if applied during the immunosuppressed period. Therefore, whenever possible, vaccinations should be administered before the period of immunosuppression starts – or caught up later during the period of minimal possible immunosuppression. Nevertheless, the benefit conveyed through vaccines is undisputed, particularly if indications regarding dosing of vaccines (amount and frequency of doses) are optimized according to the given state of immunosuppression. Live attenuated vaccines are contraindicated during severe immunosuppression. Serologies should still be analysed and documented however, since these vulnerable patients require passive immunization through specific or standard intravenous immunoglobulins in case of relevant exposure to the respective antigens. For all patients therefore, careful documentation and communication of previous vaccinations and serologies (protective or not) among the various medical specialties is required to optimize patient management. For all immunosuppressed patients the efficacy of polysaccharide vaccines (such as the pneumococcal and meningococcal vaccines PSV-23 and MPV-ACWY) is strongly reduced compared to the conjugated ones (PCV13 and MCV-ACWY). Therefore, contrary to most other national guidelines, the Swiss guidelines recommend to use only the conjugated versions in primary vaccination series as well as in boosters – this applies strongly for immunosuppressed patients, but is recommended also for the general population in Switzerland. Another common management recommendation specific for transplant patients is the indication to control vaccine efficacy by measuring titers. This is also indicated for hepatitis B in HIV-positive patients, but not required for any vaccine in asplenic patients. In summary, vaccines pose an important opportunity for primary and secondary prevention for vulnerable patients at highest risk of experiencing the worst forms of the diseases to be prevented.

THU-154 - Hepatitis E ORF2 Antigen Levels Differentiate between Acute and Chronic Course of Infection

THU-154 - Hepatitis E ORF2 Antigen Levels Differentiate between Acute and Chronic Course of Infection

Staphylococcus aureus isolates from chronic osteomyelitis are characterized by high host cell invasion and intracellular adaptation, but still induce inflammation

Osteomyelitis is a severe inflammatory disease of the bone that is mainly caused by Staphylococcus aureus. Particularly, bone infections are difficult to treat and can develop into a chronic course with a high relapsing rate despite of antimicrobial treatments. The complex interaction of staphylococci with osseous tissue and the bacterial ability to invade host cells are thought to determine the severity of infection. Yet, defined bacterial virulence factors responsible for the pathogenesis of osteomyelitis have not been clearly identified.The aim of this study was to detect S. aureus virulence factors that are associated with osteomyelitis and contribute to a chronic course of infection. To this purpose, we collected 41 S. aureus isolates, each 11 from acute osteomyelitis (infection period less than 2 months), 10 from chronic osteomyelitis (infection period more than 12 months), 10 from sepsis and 10 from nasal colonization. All isolates were analyzed for gene expression and in functional in-vitro systems. Adhesion assays to bone matrix revealed that all isolates equally bound to matrix structures, but invasion assays in human osteoblasts showed a high invasive capacity of chronic osteomyelitis isolates. The high invasion rate could not be explained by defined adhesins, as all infecting strains expressed a multitude of adhesins that act together and determine the level of adhesion. Following host cell invasion isolates from chronic osteomyelitis induced less cytotoxicity than all other isolates and a higher percentage of Small-colony-variant (SCV)-formation, which represents an adaptation mechanism during long-term persistence. Isolates from acute and chronic osteomyelitis strongly produced biofilm and highly expressed agr and sarA that regulate secreted virulence factors and induced an inflammatory response in osteoblasts. In conclusion, chronic osteomyelitis isolates were characterized by a high host cell invasion rate, low cytotoxicity and the ability to persist and adapt within osteoblasts. Furthermore, isolates from both acute and chronic osteomyelitis strongly produced biofilm and induced high levels of host cell inflammation, which may explain tissue destruction and bone deformation observed as typical complications of long-lasting bone infections.

Slime production and biofilm forming ability by Staphylococcus aureus bovine mastitis isolates

Some Staphylococcus aureus strains, identified as causative agents of mastitis in cattle, exhibit the ability of producing a viscous extracellular polysaccharide layer (slime), which is nowadays considered to be a virulence factor, as it promotes bacterial adhesion onto the mammary epithelial cells and protects bacteria from opsonization and phagocytosis. Some strains of this genus are believed to exist in the form of a biofilm in the udder tissue, which may partly explain frequent therapeutic failures and a chronic course of infection. In this study we investigated the ability of slime production and biofilm formation in 70 subclinical and clinical bovine mastitis isolates S. aureus. Slime production was determined from colony morphology of isolates in Congo red agar. The ability of biofilm formation was assessed in a quantitative assay using a microtiter-plate test involving crystal violet staining and for selected strains, scanning electron microscopy on stainless steel coupons was done. Eight S. aureus isolates (11.42%) formed black colonies of dry consistency, characteristic for slime-producing strains. According to the result of microtiter plate test, 9 isolates (12.86%) were categorized as strong biofilm producers, 21 (30%) as moderate, and 40 (57.14%) as weak biofilm producers. Scanning electron microscopy revealed differences between investigated isolates with respect to their ability to colonize stainless steel surfaces and to form a three-dimensional biofilm structure.

CTL quality and the control of human retroviral infections

The CTL response plays a central part in deciding the outcome of viral infections. Evidence from host and viral genetics, gene expression microarrays and assays of T-cell phenotype and function indicate that individual differences in the efficiency of the virus-specific CTL response strongly determine the outcome of infection with the human retroviruses HTLV-1 and HIV-1. It is now believed that differences in anti-viral CTL efficiency or "quality" at the single-cell level are critical in determining the efficacy of the host response to viruses. However, it is difficult to identify and quantify the reasons for this apparent individual variation in CTL efficiency, because of the chronic course of infection and the dynamical complexity of the equilibrium that is established between the virus and the host immune response. Specifically, it is unclear whether the observed variations among infected hosts, i.e. in the frequency, phenotype and function or quality of T cells, are the causes or effects - or both - of the variation in the efficiency of virus control.

Characterization of cytokine expression in milk somatic cells during intramammary infections withEscherichia coliorStaphylococcus aureusby real-time PCR

The expression of inflammatory cytokines, including interleukin (IL)-6, IL-8, IL-12, granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma, by milk somatic cells was characterized by real-time polymerase chain reaction (PCR) in dairy cows experimentally challenged with either E. coli (n = 8) or S. aureus (n = 8). The mRNA abundance of a target gene was calibrated with that of a reference gene (beta-actin) and expressed as fold of induction over the control quarter at each time point. At no single time point did all eight quarters challenged with the same type of bacteria demonstrated increased expression of a target gene and there was large variation among animals at each given time. As a consequence, most tested comparisons were not statistically significant except the peak time points of IL-8 expression (75- and 29- fold in glands challenged with E. coli and S. aureus, respectively). However, the average fold induction of all targeted cytokines was increased in response to both bacterial challenges with the exception of IFN-gamma. The expression of IFN-gamma was only increased in milk somatic cells isolated from E. coli, but not S. aureus, challenged mammary glands. Moreover, upregulated expression of cytokine genes had higher magnitudes and/or faster responses in glands challenged with E. coli in comparison with those challenged with S. aureus. We propose that the compromised upregulation of inflammatory cytokines in S. aureus infected glands may, at least partially, contribute to the chronic course of infection caused by this pathogen. Further research on identifying factors responsible for the differentially expressed cytokine profiles may be fundamental to developing strategies that mitigate the outcome of bovine mastitis.

Classical swine fever (CSF) marker vaccine: Trial I. Challenge studies in weaner pigs

Two commercial marker vaccines against classical swine fever virus (CSFV) and companion diagnostic tests were examined in 160 conventional pigs. To test the vaccines in a “worst case scenario”, group of 10 weaners were vaccinated using a single dose of an E2 (gp55) based vaccine at days −21, −14, −10 or −7, and subsequently challenged at day 0. The challenge virus was CSFV 277, originating from a recent outbreak of classical swine fever (CSF) in Germany. In all groups, only 5 out of 10 pigs were challenged; the remaining 5 pigs served as vaccinated contact controls. Also, three control groups, each consisting of 10 non-vaccinated pigs, were challenged in parallel to the vaccinated animals. CSFV could be isolated from all non-vaccinated pigs. Among these pigs 40% displayed a chronic course of the infection (virus positive for more than 10 days). Pigs vaccinated 21 or 14 days before challenge displayed no clinical signs of CSFV after challenge. However, they were still able to replicate CSFV when challenged, as measured by reisolation of CSFV from leukocytes of the directly challenged pigs. CSFV could be isolated from the leucocytes of 25% of the pigs vaccinated 21 days before challenge and 50% of the pigs vaccinated 14 days before challenge. Chronic infection was not observed, but transmission to one vaccinated contact pig occurred. From all pigs vaccinated 10 or 7 days before challenge, CSFV could be reisolated. We observed a chronic course of infection in 5% of pigs vaccinated 10 days before challenge and in 30% of pigs vaccinated 7 days before challenge. The mortality rate was 20% in the pigs vaccinated 10 days before challenge, and varied between 20 and 80% in pigs vaccinated 7 days prior to challenge. The contact animals had lower mortality (0–20%) than directly challenged pigs, probably mirroring the delayed time point of infection. There was thus some protection against clinical illness by both marker vaccines, but not a solid protection against infection and virus shedding. The efficacy of the vaccine was best if used 3 weeks before challenge and a clear correlation between time interval from vaccination to challenge and the level of virus shedding was observed. Each vaccine had its own accompanying discriminatory ELISA, but 18% of the virus positive pigs never seroconverted in these tests.

GB virus B as a model for hepatitis C virus.

GB viruses A and B (GBV-A and GBV-B) are members of the Flaviviridae family and are isolated from tamarins injected with serum from a human hepatitis patient. Along with a related human virus, GB virus C, or alternatively, hepatitis G virus (GBV-C/HGV), the three viruses represent the GB agents. Of the three viruses, GBV-B has been proposed as a potential surrogate model for the study of hepatitis C virus (HCV) infections of humans. GBV-B is phylogenetically most closely related to HCV and causes an acute, self-resolving hepatitis in tamarins as indicated by an increase in alanine aminotransferase and changes in liver histology. Similarities between GBV-B and HCV are found at the nucleotide sequence level with the two viruses sharing 28% amino acid homology over the lengths of their open reading frames. Short regions have even higher levels of homology that are functionally significant as shown by the ability of the GBV-B NS3 protease to cleave recombinant HCV polyprotein substrates. The shared protease substrate specificities suggest that GBV-B may be useful in testing antiviral compounds for activity against HCV. Although there are numerous similarities between GBV-B and HCV, there are important differences in that HCV frequently causes chronic infections in people, whereas GBV-B appears to cause only acute infections. The acute versus chronic course of infection may point to important differences between the two viruses that, along with the numerous similarities, will make GBV-B in tamarins a good surrogate model for HCV.

Increased expression of Fas ligand on Mycobacterium tuberculosis infected macrophages: a potential novel mechanism of immune evasion by Mycobacterium tuberculosis?

We have studied the location and mechanism of apoptosis within the granulomas in the lungs at various stages of slowly progressive primary murine Mycobacterium tuberculosis infection. Parallel sections were analyzed for detection of mycobacterial antigens, Fas, and Fas ligand (FasL) by immunohistochemistry, and for apoptotic cells by terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) method. The frequency of apoptosis was high in the macrophage aggregates as compared to the lymphocyte aggregates and at the interface between them. Five to seven percent of the vacuolated macrophages in the granulomas expressed FasL intensely. These cells contained large amounts of mycobacterial antigens. These findings suggest that M. tuberculosis infection can induce increased expression of FasL in a population of infected macrophages. As a consequence the infected macrophages will be protected from the attack of cytotoxic T cells and activation of bactericidal mechanisms by Th1 type lymphocytes. This constitutes a novel evasion mechanism for M. tuberculosis possibly explaining the chronic course of infection.

EFFECT OF REPEATED SUPERINFECTION UPON THE POTENCY OF IMMUNE SERUM OF MONKEYS HARBORING CHRONIC INFECTIONS OF PLASMODIUM KNOWLESI

Protection tests have been utilized to determine the effect of superinfection upon the potency of immune serum of monkeys with chronic Plasmodium knowlesi infections. The results of these tests showed that: 1. In 2 groups of monkeys with comparable P. knowlesi infections the immune serum of 8 monkeys which had been superinfected on 7 separate occasions over a period of 2 months was much more potent than the immune serum of a group of 7 monkeys which were allowed to continue their chronic course of infection without superinfection. 2. After a series of 9 more intense superinfections the serum from the same 2 groups of monkeys contained no demonstrable protective antibodies. 3. The serum from 8 of the 10 monkeys in the original 2 groups showed a relatively high concentration of protective antibodies following a month's rest and a single superinfection. 4. The results of the experiments indicate that it is possible to increase the potency of immune serum by superinfection, but it is also possible to obtain a decrease in the protective property of the serum by too severe superinfections.