Defects In Host Defense Mechanisms Research Articles

Pattern of bacterial and fungal pathogen in patients with high risk for invasive fungal disease in an indonesian tertiary care hospital: an observational study.

IntroductionIn critically ill patients, there is a defect in host defense mechanism resulting in increased susceptibility to bacterial and fungal infection. The pattern of organisms causing infections varies between different countries and hospitals; therefore it is important that every hospital generates antibiograms to guide healthcare professionals during treatment with optimal choice of antibiotics. Our study aimed to described the pattern of fungal and bacterial pathogen in patients with high risk for invasive fungal disease (IFD).MethodsAn observational study was conducted in Cipto Mangunkusumo Hospital, Jakarta, Indonesia, within March-September 2015. Specimens were taken from blood, sputum, endotracheal aspiration, bronchoalveolar lavage (BAL), urine, pus and drainage fluid/surgical tissue specimen on 5th-7th day of hospitalization. Samples were cultured onto suitable culture media and bacterial isolates were identified using standard biochemical methods.ResultsBacteria and Candida sp. were isolated from 153 patients. C. tropicalis (44.31%) was the commonest fungal isolated. Incidence of gram-negative bacteria was higher than gram-positive bacteria. Klebsiella pneumonia was the most common gram-negative bacteria isolated, where as Enterococcus faecalis for gram-positive bacteria.ConclusionCritically ill patients were vulnerable to contracted fungal and bacterial pathogen. Candida non-albicans and Gram-negative bacteria were the most common pathogen detected among critically ill patients with high risk for IFD.

Recognition of mucin components by Pseudomonas aeruginosa.

Pseudomonas aeruginosa remains one of the most important bacterial pathogens in lung diseases and especially in Cystic fibrosis. This unusual predilection is best explained by the existence of defects in host defense mechanisms as resulting from the genetic lesion and the presence of a specific colonization niche within the lungs. The niche has been identified as the mucus layer wherein mucin glycoproteins provide a substrate for binding and allows the persistence of this organism in this milieu by a number of possible mechanisms. While this organism is capable of binding to non CF mucins, it is perhaps a combination of factors e.g. increased binding and decreased mucociliary clearance that is responsible for this marked state of colonization in CF. The organism uses chiefly proteins of its flagellar apparatus to initiate this binding and recognizes a variety of oligosaccharides that have been identified in mucins. Among these are both, neutral oligosaccharides and several forms of acidic oligosaccharides derived from the Lewis antigens. There are more than likely a larger repertoire of receptors than those identified and certainly more adhesins present than those currently known. However, the information gathered to date provides an excellent example of the specificity of bacterial interactions with mucins that will certainly be expanded as we study more pulmonary pathogens.

Current Approach to the Management of Neutropenia

Neutrophils have a critical role in host defense. Reduction in the absolute neutrophil count to below 1,000/μL is associated with increased susceptibility to infection. The pattern of infections depends on the severity and the duration of neutropenia and other associated defects in host defense mechanisms and exposure to antibiotics and other drugs, particularly corticosteroids and immunosuppressive agents. Breaks in the integrity of the skin or the gastrointestinal mucosal surfaces serve as the portals of entry for the majority of infecting organisms. Empiric antibiotic therapy and hospitalization are almost always required for the management of fever (temperature >38.2°C) in a neutropenic patient. A single antibiotic (e.g., ceftazidime or imipenem) or a combination of antibiotics with activity against both gram-positive and gram-negative organisms usually provides effective antimicrobial therapy. In low-risk patients, trials of out-patient therapy are ongoing. When febrile neutropenia does not respond to empiric broad-spectrum antibacterial therapy, fungal infections, particularly Candida and Aspergillus, should be considered, and antifungal therapy should be initiated. Recently, availability of the hematopoietic growth factors, particularly G-CSF and GM-CSF, have changed the approach to prevention and treatment of neutropenia. Randomized controlled studies have established that these growth factors accelerate hematopoietic recovery following chemotherapy and bone marrow transplantation. By shortening the duration of neutropenia, many of the heretofore inevitable problems with fever and infection can be avoided. The only major factor limiting the use of these agents is their cost. Despite the use of these growth factors, some patients will still experience slow hematopoietic recovery. For these patients, use of neutrophil transfusions, possibly from G-CSF-stimulated normal donors, may prove to be a useful adjunctive therapy.

Candida albicans in Patients with the Acquired Immunodeficiency Syndrome: Absence of a Novel or Hypervirulent Strain

To determine whether Candida albicans in patients with AIDS represents a unique strain, C. albicans isolated from 24 patients with AIDS was compared with Candida isolated from 23 healthy adults. Resistance to 5-fluorocytosine, synthesis of amino acids and nucleotides, sugar use, and enzyme activity patterns were similar among isolates from the two groups. Molecular analysis revealed similar banding patterns of EcoRI restriction fragments of DNA between 2.5-3 and 6-7 kb. In addition, the frequency of a dimorphic 3.7-versus 4.2-kb band, identified by agarose gel electrophoresis and by probing Southern transfers of EcoRI digests with a cloned fragment of C. albicans DNA encoding 25S ribosomal RNA, was not significantly different between the AIDS-derived and control C. albicans. C. albicans isolated at different time points in the course of disease and from different sites in individual patients showed identical DNA fingerprints. The similarity in isolates of C. albicans that cause disease in AIDS patients and those present in healthy subjects suggests that the candidiasis associated with AIDS is not due to the presence of a unique or particularly virulent strain but is likely the consequence of a defect in host defense mechanisms.

Immune response to fungal infection.

In general, fungi are saprophytes that are well adapted to grow in nature supported by diverse nutritional substrates. For fungi, in contrast to many other microorganisms that infect humans, parasitism is an accidental phenomenon rather than an obligatory requirement for survival. Thus, with progressive improvement in our capabilities to prolong survival of patients with global defects in host defense mechanisms, clinical experience suggests that human tissues may support growth of numerous species of saprophytic fungi that share the capacity to grow at 37 degrees C. Normally, however, a broad array of natural and acquired host defense mechanisms make the occurrence of progressive, systemic, life-threatening mycoses extremely rare events. When one or another of these host defense mechanisms is compromised, one of a variety of significant fungal infections may then progress. Mycoses may be broadly categorized into those controlled largely by natural cellular defenses vs. acquired cell-mediated immunity. Notwithstanding data that permit such general classification of host factors controlling one or another invasive mycosis, the diverse structural and antigenic properties of individual fungi create unique patterns of infections in individual, characteristic host settings. Thus, while some broad generalizations are possible, definition of predisposing factors for specific individual mycoses (and, ultimately, prospects for corrective immunotherapy) requires careful characterization of diverse features of fungal forms mediating divergent immune responses.

Listeria monocytogenes cerebritis, bacteremia, and cutaneous lesions complicating hairy cell leukemia

Hairy cell leukemia is a lymphoreticular malignancy characterized by a chronic course and multiple defects in host defense mechanisms. Infections are the major cause of morbidity and mortality in this malignancy. Opportunistic infections due to pathogens normally controlled by cell-mediated immune mechanisms have been increasingly described but have not included listerial infections. This report describes a case of disseminated listeria monocytogenes infection including the uncommon manifestations of cerebritis and cutaneous lesions in a patient with hairy cell leukemia.

Overview of the problem of infections in the immunocompromised host

The term immunocompromised is imprecise and, in its broadest usage, could include, among others, the elderly, post-operative patients, and patients with diabetes or cancer. Even when used in a more restrictive manner, it is important to recognize that there are many components incorporated into the system of host defense mechanisms. Deficiencies in different components may make the host susceptible to quite different infectious complications. Table I lists diseases and therapeutic measures that are associated with alterations in host defense mechanisms. Each specific defect predisposes to specific predominant infectious complications. For example, patients who are unable to produce normal immunoglobulins are more susceptible to gram-positive coccal infections, whereas patients with impaired cellular immunity are more susceptible to intracellular pathogens. Therefore, it is important to identify the specific impairment in host defense mechanisms in order to recognize those organisms that are most likely to cause infection. Neutropenia probably is the most common and most important factor predisposing to infection. It is the major defect in host defense mechanisms in patients with acute leukemia and in patients during the early stages after bone marrow transplantation. Moreover, neutropenia is a frequent additional factor predisposing to infection in patients with other deficiencies in host defense mechanisms. For example, patients with chronic lymphocytic leukemia may have hypogammaglobulinemia as their only deficiency during the early stages of their disease, but neutropenia emerges as the predominant deficiency in the advanced stages of this disease. The major factor predisposing patients with acquired immunodeficiency syndrome to infection is impaired lymphocyte function, but

SIMULTANEOUS OCCURENCE OF RECURRENT MENINGITIS AND EPIGLOTTITIS CAUSED BY IDENTICAL STRAINS OF HAEMOPHILUS INFLUENZAE TYPE b IN SIBLINGS WITH COMPLEMENT DEFICIENCY

Unusual presentation of infections by encapsulated microorganisms suggests the presence of either particular microbial virulence or a defect in host defense mechanisms. In a native Swiss family of unrelated parents we investigated the organisms of recurrent meningitis in a 2 y old girl and of epiglottitis in her 6 y old brother occuring simultaneously with the 2nd episode of meningitis. Serotyping, biotyping and analysis of outer membrane proteins by SDS-polyacrylamide gels revealed identical strains of H. influenzae type b, biotype I, which was also recovered from the nose of an additional healthy brother. Complement analysis revealed complete isolated deficiency of C2 in both affected children (homozygotes) and decreased C2 levels in both parents (heterozygotes).In conclusion, the same organisms were responsible for 2 episodes of recurrent meningitis and a secondary case of epiglottitis. Even though recurrence and contagiousness of systemic H. influenzae type b disease do not implicate complement deficiency, search for immune defects is warranted in such conditions.

Impairment of hemolytic complement activation by both classical and alternative pathways in serum from patients with kwashiorkor

MANY DIVERSE DEFECTS in host defense mechanisms have been described in children with severe protein-energy malnutrition? 3 A consistent finding has been a reduction in classical pathway hemolytic complement activity, ~,2 diminished concentration of all classical pathway components except C4, 4 and evidence of in vivo complement activation (including the demonstration of C3 breakdown products and immunoconglutinin, an antibody to activated C423 complexes, in serum? Much less has been reported about a!ternative pathway activity in PEM, 6,v although this mechanism may be of considerable importance in defense against gram-negative bacteria, a common cause of terminal sepsis in PEM? We assessed both pathways of complement activation and serum opsonic activity in patients with acute PEM and observed changes with nutritional rehabilitation.

Suppressor cells in coccidioidomycosis

Patients with coccidioidomycosis manifest a wide variety of severity of infection. Patients with unifocal and particularly multifocal dissemination manifest a defect in host defense mechanisms. This study focuses on the in vitro response to PHA as an indicator of immunoregulatory mechanisms. Study subjects are divided into four groups: Group I—17, patients with active disseminated coccidioidomycosis and lesions in multiple organs; Group II—15, patients with active disseminated coccidioidomycosis and a single lesion; Group III—16, patients with active coccidioidomycosis confined to the lungs; and Group IV—18, patients in whom coccidioidomycosis is inactive. The response to PHA was heterogeneous, even within groups. When cells were cultured in the presence of indomethacin or R020-5720, Group I cells demonstrated highly significant augmentation of the response to PHA ( P < 0.002), whereas cells from Groups II to IV were unaffected. When adherent cells were removed by passage through a nylon wool column, the effect of indomethacin could no longer be demonstrated. Direct measurement of prostaglandin production (PGE 2 and PGF 2α) and thromboxane suggest that there is no difference in the quantity of these compounds produced by unstimulated or PHA-stimulated cells by Group I versus Group IV cells ( P = 0.2-0.4). Indomethacin or R020-5720 markedly inhibit the production of these compounds. Studies of the effect of exogenous prostaglandin on PHA-stimulated cells suggest that Group I cells may be more inhibited by PGF 1α and PGF 2α compared to Group IV cells. The data demonstrate that PHA cultures of cells from Group I patients are suppressed. The suppressor cell can be removed by adherence to nylon wool and is inhibited by indomethacin or R020-5720.

Granulocyte function in patients with chronic renal failure: surface adherence, phagocytosis, and bactericidal activity in vitro.

The defects in host defense mechanisms that explain the enhanced susceptibility to infection of patients with chronic renal failure are not understood, and previous studies concerning function of polymorphonuclear leukocytes (PMNL), the major antibacterial defense, conflict. Therefore, the antimicrobial functions of PMNL obtained from chronically uremic patients and serum factors essential for PMNL activity were evaluated. The potential modifying effect of high concentrations of serum from uremic patients on PMNL of uremic patients was determined, and granulocyte adherence, an activity related to recruitment of cells to inflammatory sites, was measured. Phagocytosis of 14C-labeled Staphylococcus aureus and bactericidal activity were normal and unaffected by high concentrations of uremic serum. Serum from uremic patients opsonized staphylococci and yeast normally. Oxidative metabolism of PMNL [14C-1]glucose oxidation, O2 consumption, and quantitative protein iodination) was normal, as was PMNL adherence. If the uremic patient has an increased risk of infection, this risk cannot be ascribed to defects of PMNL responses that have been studied in these patients.

PROTEIN CALORIE MALNUTRITION AND INFECTION WITH HEPATITIS-ASSOCIATED ANTIGEN

The incidence of hepatitis-associated antigen (HAA) in normal Thai adults is approximately 10%. When Thai children were studied for the age-specific prevalence of serum hepatitis-associated antigen it was found that the adult frequency is reached at about the age of 5 years. Children below this age showed a lower prevalence, with serum hepatitis-associated antigen being significantly more common in boys. In young children with severe protein-calorie malnutrition, however, serum HAA was found in 29% of 48 patients during their eight-week hospitalization, with no sex-difference in the incidence of antigenemia. In three of the four patients who were antigenemic throughout the period of observation the titer of serum hepatitis-associated antigen declined significantly as the patients' nutritional status improved. It is suggested that undernutrition and its associated defects in host defense mechanisms contributes to an increased susceptibility to infection with hepatitis-associated antigen. This may in part help to explain the relatively high prevalence of hepatitis-associated antigen infection as found in tropical countries.

Type b haemophilus influenzae infections in adults.

The paper by Norden, Callerame and Baum in this issue of the Journal calls attention to a facet of Haemophilus influenzae infections that has aroused only sporadic interest in the past. Although this kind of disease has been known to occur in adults for many years, the few cases in this age group have stimulated the description of single ones and the association of its pathogenesis with either a local or a generalized defect in host defense mechanisms. Thus, many reports have emphasized the relation of susceptibility to this type of infection to deficient or defective immunoglobulins, antibiotic-therapy (superinfection), spinal . . .