More than 2 lobar pneumonias make it necessary to rule out an immunologic deficit.

A 43-year-old man consults for diarrheal syndrome, and refers among his history 3 pneumonias in adulthood. Which of the following immunological studies should we request:

Serum immunoglobulin count and antibody production capacity test.

Phagocytosis test and oxidative metabolism of neutrophils.

Apoptosis test (programmed cell death) in the patient's circulating lymphocytes.

Study of the repertoire and clonality of T lymphocytes (alpha/beta).

In this patient it would not be appropriate to request any immunological study.

[A case of autoimmune lymphoproliferactive syndrome and literature review].

To summarize the clinical characteristics, diagnosis and treatment of a case with autoimmune lymphoproliferative syndrome (ALPS) . The patient was diagnosed as autoimmune lymphoproliferactive syndrome (ALPS) after being admitted to the Department of Rheumatism and Immunology of Tianjin Children's Hospital in February 20, 2014. The clinical characteristics, physical examination, laboratory tests, gene tests, and treatment process were analyzed and related literature was reviewed. The patient was a 16-month- old boy.Since the first month of life, he started to have repeatedly fever, diarrhea, shortness of breath, lymphadenopathy, hepatosplenomegaly, anemia (HGBmin 50 g/L) and thrombocytopenia (min 35 × 10⁹/L) . But multiple exams showed a normal peripheral blood leukocyte count, hypergammaglobulinemia (IgG 19 800 mg/L, IgA 1 710 mg/L, IgM 2 590 mg/L) and significantly increased serum vitamin B12. Flow cytometric measures showed that CD3⁺ CD4⁻ CD8⁻ T lymphocytes significantly increased ( > 10%) at four times. The count of CD3⁺ TCRαβ⁺ CD4⁻ CD8⁻T lymphocytes (double negative T cells; DNTs) >3% twice. The genetic test showed that 309th FAS gene area showed heterozygous mutations, the boy was diagnosed as ALPS. Added examinations of lymphocytes apoptosis induced by FAS was positive. He was treated with prednisone 15 mg once daily and immunomodulator 150 mg three times a day, while in maintaining period with normal levels of hemoglobin and platelet, the dose of prednisone was reduced gradually. Till now, the patient has been treated and observed for 8 months. We retrieved the reports of ALPS in the databases at home and abroad published in recent 10 years, more than 400 cases reported from foreign countries, but there were only 5 domestic cases. Among those, 4 had onset in infancy and 1 at 6-years of age. All the cases presented servere lymphadenopathy and hepatosplenomegaly with anemia (4 of them with hemolytic anemia) and thrombocytopenia. Three cases had a history of frequent infection, one of them had glomerulonephritis. All patient with significant high level of serum immunoglobulin ( > 1.5 times upper limit of normal range), in 3 of them serum vitamin B12 was > 1.5 pg/L (the other 2 cases missed the exam). In 5 cases CD3⁺ CD4⁻ CD8⁻T cells > 10%, and in 2 case DNTs were 8.9% and 15.7% respectively (the other 3 cases missed the exam). Three cases were clearly detected with FAS mutations. All patients were treated with corticosteroid, 2 of them were added with mycophenolate mofetil. The therapy presented effective result in early 1-3 months, but no long-term follow-up reports were available. ALPS is a disorder of disrupted lymphocyte homeostasis caused by defective Fas-mediated apoptosis, and it is one of the primary immunodeficiency diseases. The onset of the disease occurs during infancy mainly. Clinical lymphoid hyperplasia and autoimmune phenomena are outstanding signs, which can be associated with frequent infections and allergies. The level of serum vitamin B12 > 1.5 pg/L and the count of CD3⁺ CD4⁻ CD8⁻ T cell show important significance. Exact diagnosis should depend on detecting DNTs and FAS gene.

5'-nucleotidase

The test may also be referred to as 5'NT Levels Blood Test, CDF73 Levels Blood Test, and Ecto-5'-Nucleotidase Levels Blood Test. Lymphocyte 5'nucleotidase in immunological disorders Ecto-5'Nucleotidase is considered a maturation marker for T cells and B cells. This is due to the fact that the enzyme activity is approximately 10-times higher for peripheral T cells than thymocytes, 5-6 times higher in adult peripheral B cells than fetal B cells, and largely absent in non-T cell and non-B cell lymphocytes. In immunodeficiency diseases with arrested lymphocyte maturation, ex-5'nucleatidase activity is generally low. Such diseases include severe combined immuno-deficiency, Wiskott–Aldrich syndrome, congenital X-linked agammaglobulinemia, selective IgA deficiency and acquired immune deficiency syndrome (AIDS).

Lymphocyte subsets, immunoglobulin levels, complement activity CH50, and phagocytic peroxide production in 19 Iranian patients with first episode of bacterial meningitis.

Despite the availability of potent antimicrobial drugs, bacterial meningitis remains a serious infection with significant morbidity and mortality. In many studies, pyogenic meningitis is reported in patients with immunoglobulin (Ig) and complement deficiencies. In the present study, a broad range of immunological tests were performed to determine the relative importance of primary immunodeficiency as a predisposing cause of first episode of pyogenic meningitis without any evidence of other major infections in past medical history. We studied 19 patients with bacterial meningitis confirmed by smear, culture, and cerebrospinal fluid parameters. Immunological tests were performed within 1 to 21 days of diagnosis. Twenty healthy adults served as controls. Serum Ig levels (IgA, IgG, IgM, IgE) and total hemolytic complement (CH5O) as screening tests were done. Lymphocytes, neutrophils, and T-cells were enumerated. Nitroblue tetrazolium test was used for the assessment of neutrophil function. Thirteen patients were male and six were female. The mean age of the patients was 27.8 ± 19 years (range 5-73 years). One patient had subnormal IgA levels; five patients had subnormal IgE levels; one patient had lymphopenia and low CD4, CD3, and CD19; and one patient had subnormal IgM and IgE levels with lymphopenia and low CD4, CD3, CD8, and CD19 counts. All patients had normal complement components (C3 and C4), CH50, and nitroblue tetrazolium test. The most common immunodeficiency in our study was Ig deficiency. Our results support the recommendation that immunological evaluation, especially Ig assay, should be used in patients with bacterial meningitis even in the first episode.

Caspase-8 deficiency

Diagnosis Clinical features suggesting CEDS should be investigated by immunologic studies assessing serum immunoglobulin levels, antibody function, and lymphocyte activation. Patients with CEDS have hypogammaglobulinemia, make poor antibody responses to pneumococcal polysaccharide antigens, and their B cells, T cells, and NK cells do not activate well to stimuli. Treatment Given the rarity of this condition, the prognosis and optimal treatment are unclear. Patients who have CEDS have done well while maintained on intravenous immunoglobulin and prophylactic acyclovir to decrease sinopulmonary infections and mucocutaneous herpes virus outbreaks. Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder. References External links Autosomal recessive disorders Immune system disorders

[Programmed death (apoptosis) of T CD4 lymphocytes and AIDS pathogenesis].

A major characteristic of human immunodeficiency virus (HIV) infection is progressive decline in T CD4+ lymphocytes. Ten years after infection, on average, this cell subpopulation disappears and AIDS develops. In the asymptotic phase T CD4+ lymphocytes no longer respond, in vitro or in vivo, to certain memory antigens constrained by the class II histocompatibility complex, or in vitro to polyclonal activators like pokeweed mitogen. They retain, however, some proliferative response activity and constitute only a small proportion of the T CD4+ population. Indirect mechanisms of depletion are therefore sought. We have proposed a hypothesis for a single mechanism: a programmed death process, apoptosis, reactivated in mature T CD4+ lymphocytes of seropositives. Unlike necrosis, apoptosis has a role in embryogenesis, in the adult in certain cell populations and, in immature thymocytes, in T lymphocyte selection and establishment of self-tolerance. T CD4+ lymphocytes of infected subjects lose their ability to proliferate in vitro, as they undergo a form of suicide in response to certain stimuli. In vivo T CD4+ cell activation induced by various infectious agents, including HIV, progressively reduces the subpopulation, independently of the virus' cytopathogenic effect. Tests were performed that explored the T CD4+ lymphocyte response to super-antigens, which mimic and amplify the effect of memory antigens by way of CMH II molecules of Ag-presenting cells and certain nu beta chains of the alpha beta receptor for the Ag which are expressed by a third of human mature T CD4+ lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Ataxia–telangiectasia

All individuals with A–T should have at least one comprehensive immunologic evaluation that measures the number and type of lymphocytes in the blood (T-lymphocytes and B-lymphocytes), the levels of serum immunoglobulins (IgG, IgA, and IgM) and antibody responses to T-dependent (e.g., tetanus, Hemophilus influenzae b) and T-independent (23-valent pneumococcal polysaccharide) vaccines. For the most part, the pattern of immunodeficiency seen in an A–T patient early in life (by age five) will be the same pattern seen throughout the lifetime of that individual. Therefore, the tests need not be repeated unless that individual develops more problems with infection. Problems with immunity sometimes can be overcome by immunization. Vaccines against common bacterial respiratory pathogens such as Hemophilus influenzae, pneumococci and influenza virus (the “flu”) are commercially available and often help to boost antibody responses, even in individuals with low immunoglobulin levels. If the

Lymphocyte population and apoptosis in the lungs of smokers and their relation to emphysema.

Previously, it had been shown that T-lymphocytes are the predominant inflammatory cells found in the alveolar wall of smokers and their numbers correlated with the extent of emphysema. However, the phenotype of these cells was not defined. The aim of this study was to describe the different T-cell phenotypes and investigate the possible presence of apoptosis in the lung parenchyma of smokers. Samples from lungs were obtained at surgery from 15 patients who smoked and six who had never smoked. Samples were frozen and prepared for histological and immunocytochemical examination. Slides were stained for CD3+, CD4+, CD8+, gammadelta T-cells, CD56 natural killers ((NK) cells), and elastase (neutrophils). Anti-CD95 monoclonal antibodies and in situ end-labelling techniques were used to detect Fas expression and apoptosis. Positive staining cells were expressed as cells-mm alveolar wall-, percentage of total cells, and Fas/APO and apoptosis index. Emphysema was identified macroscopically, microscopically and reported as present or absent. All subjects had pulmonary function tests before surgery. Neutrophils were the predominant cell in the lung parenchyma of nonsmokers and smokers without emphysema. In smokers with emphysema, the CD3+ and CD8+ were the predominant cells (p<0.05) in the alveolar wall. gammadelta cells were increased in all smokers and no increased numbers of NK cells was found. The T-cell numbers x mm alveolar wall(-1) showed a bilinear relationship with the amount smoked increasing at an inflection point of 30 packs yr(-1) (R2= 0.345; p < 0.01). Apoptosis in smokers showed a bilinear relationship with the amount smoked increasing sharply in smokers with emphysema (R2=0.3613; p < 0.009). It is concluded that the pathogenesis of emphysema might be mediated by T-lymphocytes, mainly CD8+ cytolytic T-cells, and that apoptosis might be one of the mechanisms of lung destruction leading to the development of emphysema. If this is the case, it could be speculated that T-cell inflammation is a response to antigenic stimuli originating in the lung and induced by cigarette smoking.

Douglas R. Green

Research After many studies on immunological tolerance, Green's work on cell death began with his discovery of activation-induced apoptosis in T lymphocytes, the role of c-Myc in this process and the finding that Bcl-2 cooperates with Myc in oncogenesis by blocking apoptosis. More recently, he discovered the process of LC3-associated phagocytosis, which links the autophagy pathway to phagosome maturation. Other areas of interest include regulated necrosis, metabolic reprogramming in T lymphocytes, and the function of the tumor suppressor, p53. As of 2014 he had published many chapters and books and over 500 papers, making him one of the world's most cited molecular biologists. He is listed in: ISI "highly cited" (Immunology 2003) ISI "highly cited" (Molecular Biology/Genetics 2014) Recognition

[Characteristics of immunologic test values in the elderly].

The immune system changes during the lifespan of man. Many described changes in the immune system of the elderly were dependent on illness or chronic diseases. To exclude these pathological changes in the immune system and to exclusively describe age-dependent changes, Ligthart et al. defined immunogerontological criteria to study the immune system in the elderly, the SENIEUR-Protocol. Most changes in the immune system of elderly are within the normal ranges of the appropriate parameter. However, there are many significant differences between the status of the immune system in healthy young and elderly individuals, within these normal ranges. The comparison between SENIEUR-elderly and healthy young and the additional comparison of these two groups with centenarians allows the discussion of potential pathological effects of these changes. In this article we summarize the described changes of the immune system in SENIEUR-elderly and centenarians. The serum levels of the immunoglobulins G, M and A increased with age, as well as the number of benign monoclonal gammopathies and the number of autoantibodies. The titers of zinc are significantly decreased in the serum of the elderly. The production of the acute phase protein C-reactive protein is not age-dependent, whereas the serum levels of alpha 2-macroglobulin are significantly increased in the elderly. The number of lymphocytes decreased and the number of neutrophils increased with aging. Monocytes, basophils, and eosinophils are without changes during life. There are many descriptions about changes of the leukocyte sub-population in aging, which are not always comparable. However, the number of T cells (CD3) decreases. Within the T cells the CD8 cells decreased more than the CD4 cells, resulting in an increased CD4/CD8 ratio. Memory T cells (CD45RO) increase during life, whereas naive T cells (CD45RA) decrease. Interestingly, centenarians have more naive T cells SENIEUR-elderly. The number of B cells (CD19) decreased also, whereas the number of natural killer (NK) cells (CD16, CD56, CD57) increases with aging. The capacity of leukocytes from the elderly to produce cytokines is also significantly different from those of the young. The release of the TH1-cytokines interleukin (IL)-2 and interferon (IFN)-gamma is decreased, whereas the production of the TH2-cytokines IL-4 and IL-10 is increased in the elderly. The production of proinflammatory cytokines such as IL-1, IL-6, IL-8, and tumor necrosis factor-alpha is increased in the elderly. In contrast, the capacity to produce the antiviral cytokine IFN-alpha is reduced in elderly individuals. In conclusion, the immune system shows many age-dependent changes, but we know little about the reason and the potential pathological effects of these changes.

Complement-dependent cytotoxicity

CDC assay is usually used for performing crossmatch test. The basic version involves incubation of patient’s serum with donor’s lymphocytes and second incubation after adding rabbit complement. Presence of dead cell (positive test) means that donor isn‘t suitable for this particular patient. There are modifications available to increase test sensitivity including extension of minimal incubation time, adding antihuman globulin (AHG), removing unbound antibodies before adding complement, separation of T cell and B cell subset. Besides CDC crossmatch there is flow-cytometric crossmatch available, that is more sensitive and can detect even complement non-activating antibodies. See also Contrast with antibody-dependent cellular cytotoxicity (ADCC) References Immunology

Serial tests of T-cell function predict long-term survival in an elderly cohort from a Scottish general practice.

INTRODUCTION The care of the elderly presents serious challenges to general practice. In 1979, the first author took over the care of a general practice in Scotland where 21% of registered patients were elderly. This resulted in a high workload and prompted research into how this might be mitigated. AIM To measure serial tests of T-cell function in these individuals in order to identify those whose immune response was impaired and assess the effect of this in a long term follow up. METHODS This research comprised two phases. In the assessment phase (1979-82), patients were invited to have a 3-monthly visit from a research nurse where clinical measurements were made and blood taken for immunological tests of lymphocyte proliferation after culture with phytohaemagglutinin (PHA). For each patient, all records were surveyed and problems identified. In the follow-up phase (post 1982), all deaths were assessed with complete life-long follow up. RESULTS Of 405 people originally invited to participate in this research, 314 (78%) agreed and 246 (153 female, 93 male) entered the follow-up phase and were followed for 36.5 years. Factors significantly associated with lower survival were age, male sex, diastolic blood pressure, current smoking and poor immune function, as demonstrated by the percentage of negative responses in at least six PHA tests. Considered in four groups by percentage of failing tests, the lowest group had a life span 4 years shorter than the highest (P<0.01). The four groups did not differ significantly in general practitioner workload, diagnosed problems or causes of death. DISCUSSION Poor cellular immune function was associated with poor survival over lifetime follow up of >30 years. A sensitive, specific and longitudinally consistent measure of T-cell function is required to predict who may be at risk of poorer survival within our practices.

ELISpot

More specifically, the T-cell ELISpot assay is used to characterize T-cell subsets. This is because the assay can detect the production of cytokines IFN-y, IL-2, TNF-alpha, IL-4, IL-5, and IL-13. The first three cytokines are produced by Th1 cells, while the last three are produced by Th2 cells. Measuring T-cell responses through cytokine production also makes it possible to study vaccine efficacy. With T-cell FluoroSpot, you can monitor tumor-infiltrating lymphocytes. You can also analyze the IFN-y cytokine and granzyme B secretion in order to assess cytotoxic T-cell responses. Both of these are used for cancer research. With B-cell FluoroSpot, vaccine efficacy can also be observed by quantifying the secretion of IgG, IgA, and IgM before and after a vaccination. This analysis of multiple immunoglobulins is made possible because of the fluorescence method used in the FluoroSpot. References Biochemistry methods Immunologic tests

[Diagnostic significance of immunocomplexes].

Immunocomplexes from the blood serum of 129 autopsied males and females from newborn age up to 95 years were examined by means of the PEGIKEM test. In cases of sudden death without inflammatory changes the mean value of immunocomplexes x = 22.794, s = 23.426; in cases of death due to injury without inflammatory changes x = 22.935, s = 21.947. In sudden death with inflammatory changes x = 41.154, s = 50.97; in death due to injury with inflammatory changes x = 54.500, s = 34.757. In inflammatory changes the values of immunocomplexes are increased statisticaly significantly; in sudden death p = 0.0485, in death due to injury p = 0.0193 when compared with controls without inflammatory changes. In sudden death, no statistically significant differences were found between the age groups 0-1 year, 2-15 years and above 16 years. In sudden death and that due to injury, the lowest values of immunocomplexes were found in infants to 1 year of age. Increased values of immunocomplexes may also be found in cases without inflammatory changes and, in contrast to it, may be low in inflammatory changes. Dependence of immunocomplexes upon the duration of the postmortem period was neither proved nor excluded by means of the statistical method. It is suitable to examine immunocomplexes immediately after the withdrawal of blood sample, fluctuation of values may occur in vitro (in cases of drowning and phylonephritis). The examination of immunocomplexes in postmortem blood is possible and in some cases suitably supplements the spectrum of diagnostic methods.

Lymphocyte-variant hypereosinophilia

Following the historical findings cited above, studies identified the cytokine, interleukin 5 (IL5), as the eosinophil growth-stimulating CFU made by T cells from patients suffering the idiopathic hypereosinophilic syndrome. Subsequent studies likewise identified IL5 as a cytokine being overproduced by certain lymphocytes taken from patients with lymphocyte-variant eosinophilia. These and other studies support the view that lymphocyte-variant hypereosinophilia is a unique disease characterized by hypereosinophilia secondary to the pathological production of eosinophil growth factors, particularly IL5 but possibly also IL4; IL13, and GM-CSF by one or more aberrant clones of T cells. The aberrant T cell clone, as defined by immunophenotyping their expression of certain cell surface molecules, the cluster of differentiation (i.e. CD) proteins, varies from patient to patient; furthermore, some of these clones also exhibit clonal rearrangements in their T-cell receptor gene. The most

[Use of an apoptosis test in the biological follow up of patients infected with HIV].

Among biological parameters, spontaneous apoptosis has been studied in lymphocyte culture of HIV seropositive patients. Apoptosis seems to be related with CD4+ deletion.

Tuberculosis diagnosis

Immunological test ALS Assay Antibodies from Lymphocyte Secretion or Antibody in Lymphocyte Supernatant or ALS Assay is an immunological assay to detect active diseases like tuberculosis, cholera, typhoid etc. Recently, ALS assay nods the scientific community as it is rapidly used for diagnosis of tuberculosis. The principle is based on the secretion of antibody from in vivo activated plasma B cells found in blood circulation for a short period of time in response to TB-antigens during active TB infection rather than latent TB infection. Transdermal Patch A similar approach to the ALS assay. The transdermal patch is a suggested method of detecting active M.tuberculosis circulating within blood vessels of patient. This skin patch contains antibodies recognizing the secreted bacterial protein MPB-64 passing through the blood capillaries of the skin creating an immunological response. If the patch detects this secreted bacterial protein, the surrounding skin will redden.

Immunology of Early and Late Ontogenesis.

Immunological interrelations are one of the most important factors, forming all the periods of ontogenetic body development. At early ontogenesis in the organism of mammals, including humans, the immunological tolerance is induced to own (self) antigens that prevents the development of autoimmune reactions in adult life. The system of immune recognition reaches its fine discriminative capacity in mammals and humans on the background of recognition of self HLA class I (CTL of CD8(+) phenotype) or class II (T helpers of CD4(+) phenotype). The phenomenon of major histocompatibility complex (MHC) restriction reactivity of cytotoxic T lymphocytes (CTL) makes difficult the recognition in changes or mutations in HLA system. Natural killers (NK) control constantly the structure of self MHC class I molecules, and in contrast to CTL may recognize small antigenic changes of MHC molecules, induced by viruses, mutations and transformation. Immune system aging is displayed by both quantitative, and functional changes in lymphocyte subpopulations with prevalence of T helpers type 2 over type 1 cells, responsible for the development of DTH. According to immunological theory of aging, the role of immune system cells should be taken into consideration in relation to the synthesis of activated oxygen forms with bactericidal properties by monocytes and neutrophils. Overproduction of activated oxygen radicals may result in destruction of proteins, lipids, DNA, and in the body aging. Activated oxygen radicals are one of events of lymphocyte apoptosis in aerobic conditions.

Host defensive, immunological, and microbiological observations of an early-onset periodontitis patient with virus-associated hemophagocytic syndrome.

Virus-associated hemophagocytic syndrome (VAHS) is a disorder characterized by benign generalized histiocytic proliferation and marked hemophagocytosis associated with systemic viral infection. An immunodeficiency which includes an extremely decreased leukocyte and platelet count together with abnormalities in the CD4/CD8 ratio are the most common features of VAHS. Here we report an early-onset periodontitis (EOP) patient with VAHS from the standpoint of host-parasite interaction to understand the effect of this systemic disorder which might possibly influence susceptibility to periodontal disease. The patient is a 16-year-old Japanese male clinically diagnosed as having generalized EOP with slight gingival inflammation and moderate bone loss. This patient manifested VAHS at 3 years of age, and then had an unusual 4 recurrences (at 5, 7, 11, and 14 years old). Laboratory tests conducted include: 1) complete blood analyses: 2) peripheral neutrophil functions (chemotaxis, phagocytosis, superoxide production, and adherence); 3) peripheral lymphocyte subpopulations and functions, T-cell proliferative activity and productivity of cytokines (interleukin-2 [IL-2], interferon gamma [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]); 4) serum cytokine levels (IL-1 beta, IL-2, soluble IL-2 receptor [sIL-2R], IL-4, IL-6, IFN-gamma, and TNF-alpha; 5) serum immunoglobulin G (IgG) antibody titers against periodontopathic bacteria; 6) serological human leukocyte antigen (HLA) typing; and 7) determination of bacterial flora of the periodontal pockets. The results indicated that the patient's neutrophil chemotaxis and random migration were below the normal range. In lymphocyte examinations, T-cell proliferative activity, IL-2, and IFN-gamma productivity were elevated. Serum IFN-gamma level was also significantly higher than normal range. No specific periodontopathic bacteria were predominant in the periodontal pockets, however, the serum IgG titer against Porphyromonas gingivalis was elevated throughout the examination period. It is suggested that VAHS might be a possible risk factor for periodontal disease, and hence may serve as a model in understanding the role of host defense mechanisms in the establishment of inflammatory periodontal disease.

Dock8

This disorder is considered a combined immunodeficiency because it includes both decreased lymphocyte numbers and defective lymphocyte function. It can also be classified as a type of autosomal recessive hyperimmunoglobulinemia E syndrome. Laboratory manifestations include progressive lymphopenia that primarily affects CD4 and CD8 T cell subsets, reduced B cell and/or NK cell counts in some patients, eosinophilia, and immunoglobulin abnormalities. Antibody responses to vaccines are frequently poor. Loss of Dock8 protein expression can be demonstrated by diagnostic intracellular flow cytometry testing.

Lymphoproliferative Disorders -- Evaluation

The new criteria required for the diagnosis of an autoimmune lymphoproliferative syndrome (ALPS) [6] include chronic non-malignant lymphoproliferation (lymphadenopathy or splenomegaly over six months of evolution) and elevated peripheral blood double-negative T cells (DNTs). The first accessory in diagnosis is a somatic or a germ-line mutation in ALPS causative gene ( FASL , CASP10 , FAS ) and defective in vitro Fas-mediated apoptosis. Secondary diagnostic criteria are elevated biomarkers (plasma sFASL over 200 pg/ml, plasma or serum vitamin B12 greater than 1500 ng/L, plasma IL-10 greater than 20 pg/ml, and plasma IL-18 greater than 500pg/ml) and immunohistochemical findings on biopsy consistent with ALPS. Other diagnostic signs are polyclonal hypergammaglobulinemia, autoimmune cytopenia and a family history of ALPS or non-malignant lymphoproliferation.

[Anti-HLA antibodies in nephropathic patients].

The presence of anti-human leukocyte antigen (HLA) alloantibodies in nephropathic patients is due to immunogenic stimuli such as transfusions, pregnancies, and transplantations. These stimuli can be highlighted using a classic aspecific serologic technique, such as complement-dependent cytotoxicity (CDC) or using more recent and specific techniques, such as cytofluorimetrics or enzyme linked immunoabsorbant assay (ELISA). Because the presence of anti-HLA preformed antibodies is linked to the largest incidence of both acute and chronic rejection, it seems appropriate to re-evaluate that data obtained using aspecific classic serological analysis techniques by using the more specific cytofluorimetric technique. To aid in the possible prevention of ant-HLA antibody formation, it is also appropriate to analyze the influence of immunogenic stimuli on the development of these antibodies. We studied 116 patients (37 women and 79 men). Anti-HLA antibodies were detected using microlymphotoxic technique after separation of B and T lymphocytes. This separation was obtained using magnetic balls. We used a 30-cell panel. We also used a recent cytofluorimetric test (Flow Pra screening; One Lambda Inc., 21001 Kittridge St., Canoga Park, California, U.S.A.) with a panel of micrograins covered with class I and class II purified antigens. Statistical analysis was performed using chi-square analysis or Fischer s exact test. For each test, sensibility, specificity, and positive and negative value were measured. Among 33 patients testing positive using the classic CDC-PRA technique (17 positive for B-lymphocytes and 16 positive for both B and T lymphocytes), using cytometry, 25 were positive for anti-HLA-specific antibodies (10 among the B lymphocyte-positive patients and 15 among the B + T lymphocyte-positive patients). Two patients were shown positive only using the cytofluorimetric method. Of the 27 patients positive at cytometry, 18 were positive for class I and class II, 4 for class I, and 5 for class II. FLOW-PRA screening results were less sensitive and more specific. The results obtained by the two methods are comparable(p<0.0001). The immunogenic stimuli found responsible for immunization were: transfusion in 10 of 25 patients, pregnancies in 3/9 patients, transplant in 4/8 patients, and different immunogenic stimuli in 10/12 patients. The results were not statistically significant (p>0.05). Data show that positivity for B lymphocytes obtained using CDC-PRA is not always linked to the development of anti-HLA antibodies, whereas positivity for B+T lymphocytes, obtained using CDC -PRA, is often linked to specific antibody development. Immune response is more often directed against class I and II antibodies. The specific detection of HLA antibodies using the cytofluorimetric method allows us to identify patients at risk for rejection, and it suggests that red cells should be filtrated to prevent anti-HLA immunization secondary to transfusion in transplantation candidates.

Virological failure

The progressive decline in T-CD4 + lymphocyte counts is characterized by immunologic failure. It should be considered, however, that there is a wide biological variability (individual and interindividual) in the counts of these cells, as well as laboratory variability related to the technical reproducibility of the test. There is also circadian variation of CD4 levels and therefore it is recommended that the sample for the test be obtained in the morning. Variability related to the various motifs described above may result in oscillations of up to 25% in absolute CD4 T-lymphocyte counts, with no clinical significance. It is therefore recommended that reductions greater than 25% in T-CD4 + lymphocyte counts are suspected of immunological failure and confirmation is given. References Virology

[Demonstration of a granulocyte defect in aged persons correlated with the presence of autoantibodies].

Assessment of PMN leukocyte function and search for autoantibodies were performed in 36 aged human subjects (more than 60 years of age) and in 15 younger controls (40 to 60 years of age). Autoantibodies were found in 15 of the 36 aged subjects, and in none of the controls. Leukocyte function defects were therefore correlated to old age and to markers of autoimmunity. Phagocytosis of bacteria was significantly impaired in both groups of old-aged subjects, irrespective to the presence or absence of autoimmunity. Intracellular killing of bacteria was shown to be normal in all the examined subjects. Nitroblue tetrazolium reduction by resting and latex-stimulated leukocytes was significantly impaired only in the group of old-aged subjects with autoimmunity. These leukocyte function defects are similar to those already described in human autoimmune diseases -- particularly S.I.E. -- and confirm the possible association between P.M.N. dysfunction and autoimmunity.

Pemphigoid

Indirect immunofluorescence Indirect immunofluorescence is used to detect circulating antibodies targeting the antigens at the basement membrane zone in patients with pemphigoid. In early studies using routine techniques, only one third of patient with MPP were being tested positive. Circulating IgG and IgA antibodies are found in patient's serum. To increase the likelihood of detecting circulating antibodies, human basement membrane zone-split skin and/or concentrated serum should be used. Antigen-specific serologic testing Autoantibodies directed against a variety of antigens, including BP180, BP230, laminin 332, and type VII collagen may be detected. However, this test could not be used as the only diagnostic tool for testing as ELISA testing has limited sensitivity. Treatment The factors that determine the type of therapy used for mucous membrane pemphigoid are: [1] site(s) of involvement, [2] severity of disease, [3] rate of progression.

Cytometric analysis of immunosenescence.

We have been studying the immune system of healthy centenarians for many years, and they provide the best example of successful aging. They are people who have escaped major age-related diseases and reached the extreme limit of human life in good clinical condition. In most cases, histories of centenarians reveal them to be free of cancer, dementia, diabetes, cardiovascular diseases, and cataracts. Moreover, in order to reach such an advanced age, they should be equipped with well preserved and efficient immuno- and defense mechanisms, and optimal combinations of an appropriate lifestyle and genetic background. Using this approach, several paradoxes emerged as far as the immune system of centenarians is concerned, regarding: i) humoral immunity (increase in plasma immunoglobulins and nonorgan-specific autoantibodies, decrease in B cell number and lack of organ-specific autoantibodies); ii) cellular immunity (well preserved number of "virgin" T cells, a relatively intact T cell repertoire despite a thymus involuting since puberty, increased number of cells with markers of NK activity); iii) decreased peripheral blood lymphocyte tendency to programmed cell death, associated with a well preserved mitochondria functionality and intracellular bcl-2 levels. An age-related increase in the levels of adhesion molecule present on lymphocyte plasma-membrane, accompanied by a complex reshaping of the cytokine network, must be added to this scenario. All our data fit the hypothesis that a complex, unpredicted remodeling of the immune system occurs with age. In the present review it is underlined how flow cytometry has been used to study most of the above mentioned aspects of immunosenescence, and to establish new age-related reference values.

Lactalbumin

In an open study, the clinical efficacy of whey protein (Immunocal: cysteine content; 7.6-fold that of casein) isolated from fresh milk and purified without being heated was evaluated based on liver function test, immunological parameters, plasma or lymphocyte GSH concentrations and hepatitis virus markers in 25 patients with chronic hepatitis B or C. Immunocal (12 g as protein) food (mousse) was given twice a day, in the morning and evening, for 12 weeks (test period). Casein (12 g as protein) food (mousse) was given for 2 weeks prior to the start of -supplement with Immunocal food (induction period) and for 4 weeks after the end (follow-up period). The effects of Immunocal food on various clinical parameters were examined at 4-week intervals for 18 weeks to evaluate the efficacy of Immunocal. As a result, serum ALT activity decreased in 6 of 8 patients with chronic hepatitis B 12 weeks after the start of supplement with Immunocal food. Plasma GSH concentrations were increased in 5

[Immune complexes in sudden and violent deaths].

Immunocomplexes in the blood serum of 115 autopsied subjects chosen at random were examined by means of the Pegikem test. Average values of 34.9 +/- 44.6 were found in a group of 57 suddenly died subjects while those of 51.3 +/- 76.2 were seen in a group of 58 subjects dead due to injury. The possibility of the determination of immunocomplexes for postmortem diagnosis of immune conditions are discussed.

Cancer immunology

monoclonal anti-CTLA4 and anti-PD-1 antibodies are called immune checkpoint inhibitors: CTLA-4 is a receptor upregulated on the membrane of activated T lymphocytes, CTLA-4 CD80/86 interaction leads to switch off of T lymphocytes. By blocking this interaction with monoclonal anti CTLA-4 antibody we can increase the immune response. An example of approved drug is ipilimumab. PD-1 is also an upregulated receptor on the surface of T lymphocytes after activation. Interaction PD-1 with PD-L1 leads to switching off or apoptosis. PD-L1 are molecules which can be produced by tumor cells. The monoclonal anti-PD-1 antibody is blocking this interaction thus leading to improvement of immune response in CD8+ T lymphocytes. An example of approved cancer drug is nivolumab. Chimeric Antigen Receptor T cell This CAR receptors are genetically engineered receptors with extracellular tumor specific binding sites and intracelullar signalling domain that enables the T lymphocyte activation. Cancer vaccine

[Microlymphocytotoxic test with T lymphocytes: positivity by 3 hrs incubation (author's transl)].

Some human anti-HLA-DR and anti-HLA-A,B-sera contain cytotoxins reacting with T lymphocytes in the cytotoxic test by the prolongation of the incubation time to 3 hrs, whereas in the normal cytotoxic test of 1 1/2 hr incubation antibodies are not proved. These results suggest that simultaneous testing of sera with B and T lymphocytes not always give a true image of the actual occurrence of antibodies in the serum. The cause of the phenomen and the problem of the serological character of cytotoxins are discussed.

Innate immune defect

Diagnosis Patients with innate immune defects have generally intact adaptive immune systems with normal antibodies and T-cells. The main symptom is increased level of eosinophils in the blood, but elevated immunoglobulin E (IgE) levels may also be present. The diagnosis is made in suspected patients by measuring cytokine production by white blood cells, after stimulation by bacterial products. Testing of TLR function is becoming available through commercial reference laboratories. By abnormal tests is usually made repeat testing and also genetic testing. Treatment The common treatment for these defects usually involves antibiotic therapy to treat acute infections. Prophylactic antibiotic therapy is also used. Some patients require immunoglobulin treatment. References Immunology

Comparison of automated haematology analysers for detection of apoptotic lymphocytes.

Automated haematology analysers can rapidly provide accurate blood cell counts and white blood cell differentials. In this study, we evaluated four different haematology analysers for the detection of apoptotic lymphocytes in peripheral blood: MAXM A/L Retic, H*2, Cell-Dyn 3500 and NE-8000. With the MAXM A/L Retic haematology analyser, the apoptotic lymphocyte cluster appeared below the original lymphocyte cluster on the volume/DF1, and to the right under the original lymphocyte cluster on the volume/DF2 scattergrams. With the H*2 haematology analyser, the apoptotic polymorphonuclear lymphocytes produced a higher lobularity index on the BASO channel. With the Cell-Dyn 3500 haematology analyser, the apoptotic lymphocyte cluster appeared to the right side of the original lymphocyte cluster on the 0D/10D scattergram and to the left side of the polymorphonuclear cluster on the 90D/10D scattergram. With the NE-8000 haematology analyser, the apoptotic lymphocyte cluster was not distinguishable. Thus, apoptotic lymphocytes are readily detected on scattergrams generated by selected haematology analysers.

Timeline of immunology

1945 – Coombs test antiglobulin test (AGT) 1946 – Identification of mouse MHC (H2) by George Snell and Peter A. Gorer 1948 – Antibody production in plasma B cells (Astrid Fagraeus) 1949 – Growth of polio virus in tissue culture, neutralization, and demonstration of attenuation of neurovirulence (John Enders) and (Thomas Weller) and (Frederick Robbins) 1951 – A vaccine against yellow fever 1953 – Graft-versus-host disease 1953 – Validation of immunological tolerance hypothesis 1957 – Clonal selection theory (Frank Macfarlane Burnet) 1957 – Discovery of interferon by Alick Isaacs and Jean Lindenmann 1958–1962 – Discovery of human leukocyte antigens (Jean Dausset and others) 1959–1962 – Discovery of antibody structure (independently elucidated by Gerald Edelman and Rodney Porter) 1959 – Discovery of lymphocyte circulation (James Gowans)


The negative IgM of HAV rules out 5

An interesting one that in general needs to be studied. By the form of presentation, it is clearly an acute hepatitis, so option 1 is ruled out. The negative IgM of HAV rules out 5 and the negative HBs Ag rules out 4 (to have delta virus you need surface antigen B). When having IgM anti HBc we speak of an acute hepatitis B (3), since there is a window period of negativization of the antigen.

An interesting one that in general needs to be studied. By the form of presentation, it is clearly an acute hepatitis, so [HIDDEN]. The negative IgM of HAV rules out [HIDDEN] and the negative HBs Ag rules out [HIDDEN] (to have delta virus you need surface antigen B). When having IgM anti HBc we speak of an acute hepatitis B [HIDDEN], since there is a window period of negativization of the antigen.

A man presents abruptly with asthenia and jaundice with transaminases above 2000 IU/L. Serological markers show the following pattern: anti-HAV IgM negative, HBsAg negative anti-HBc IgM positive, anti-HCV negative. What is the diagnosis?

Acute delta superinfection in a previously unrecognised HBsAg carrier with transient loss of HBsAg simulating acute non-A, non-B hepatitis.

An 18 yr old previously well male Taiwanese was admitted with malaise, anorexia, and jaundice for two weeks. Results of liver tests were compatible with acute hepatitis. On day 1, he was seronegative for HBsAg, IgM anti-HAV, IgM anti-HBc, IgM anti-CMV, and IgM EBV capsid Ab, but positive for anti-delta in association with anti-HBc and anti-HBs. At follow up on day 5 HBsAg converted to positive with decreasing titre of anti-HBs. On day 19, the titre of HBsAg increased concomitantly with loss of anti-HBs. The results of these serological profiles indicated that this patient was a previously unrecognised HBsAg carrier, who developed acute hepatitis delta virus superinfection with transient loss of HBsAg. This phenomenon should be kept in mind in the serodiagnosis of acute viral hepatitis, especially in areas of high HBV prevalence.

Fulminant hepatitis in asymptomatic hepatitis B surface antigen carriers in Greece.

Eleven male fulminant hepatitis (FH) patients (mean age: 47.7 +/- 16 years) positive for hepatitis B surface antigen (HBsAg) but negative for IgM antibody to hepatitis B core antigen (IgM anti-HBc) were admitted consecutively to the Athens Hospital for Infectious Diseases between May 1981 and November 1983. Because of the absence of IgM anti-HBc, determined by an enzyme immunoassay, these patients were considered to be HBsAg carriers with a superimposed acute hepatitis. Three of the 11 patients received immunosuppressive chemotherapy during the six months before the onset of the acute hepatitis. None of the patients was homosexual or a drug addict. Infection with hepatitis A virus (HAV), hepatitis B virus (HBV), or hepatitis delta virus (HDV) was detected with serologic markers and/or molecular hybridization techniques. Fulminant hepatitis was attributed to spontaneous reactivation of chronic hepatitis B in four patients, chemotherapy-induced reactivation of chronic hepatitis B in three patients, HDV superinfection in one patient and possible superinfection by non-A, non-B agent(s), HDV, or HDV-like agents in three patients. Reactivation of chronic hepatitis B was an important cause of apparent acute hepatitis in heterosexual male HBsAg carriers from an area with a high prevalence of HBV infection.

Diagnostic usefulness of anti-HBc-IgM and anti-HD antibodies in acute viral hepatitis.

To evaluate diagnostic improvement achieved with the determination of antibody to hepatitis core antigen of IgM type (anti-HBc-IgM) and antibody to delta antigen (anti-HD) in acute type B hepatitis, 155 patients (of whom 100 were drug addicts) were studied, using these markers in association with the classical markers of viral hepatitis (anti-HBc, anti-HBs, anti-HAV-IgM and anti-cytomegalovirus antibodies). With classical diagnostic criteria, 121 patients would have been diagnosed as having B hepatitis (HBs Ag and/or anti-HBc antibody positive without anti-HBs antibody), 33 non A non-B hepatitis (all markers negative or anti-HBc and anti-HBs positive) and 3 A hepatitis (anti-HAV-IgM antibody positive). With the current markers, 89 were B hepatitis (anti-HBc-IgM antibody positive), 18 were simultaneous B and D infections (anti-HBc-IgM and anti-HD antibodies positive), 6 were D hepatitis (anti-HBc-IgM antibody negative and anti-HD antibody positive), 39 non-A non-B hepatitis (anti-HBc-IgM, anti-HD, HAV-IgM and anti-cytomegalovirus antibodies negative) and 3 hepatitis A. Of the 121 cases initially diagnosed as B hepatitis, only 79 were actually B hepatitis, 16 were simultaneous B and D infections, 6 D hepatitis, 18 non-A non-B hepatitis and 2 A hepatitis. Of the 33 cases considered to be non A non-B hepatitis, only 21 were really non-A non-B hepatitis; 10 were B hepatitis and 2 B and D hepatitis. When anti-HBc-IgM and anti-HD antibodies were determined, the initial diagnosis was modified in 54 of 155 cases (35 p. 100).(ABSTRACT TRUNCATED AT 250 WORDS)

Infection with hepatitis A, B, C, and delta viruses among patients with acute hepatitis in Mongolia.

One hundred ten consecutive patients (60 males and 50 females; age, mean +/- standard deviation [SD], 22.6 +/- 6.4 years; range 16-48 years) who were clinically diagnosed with sporadic acute hepatitis between December 2004 and January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core (anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients (8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc IgM, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. None had IgM antibodies to hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were diagnosed as having acute hepatitis of type A, B, C, type B + D (HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all 32 HDV isolates were classified into genotype I. The distribution of HBV genotypes among the 67 HBV isolates was A (1.5%, n = 1) and D (98.5%, n = 66). The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are prevalent among young adults in Mongolia.

The etiology of acute hepatitis superimposed upon previously unrecognized asymptomatic HBsAg carriers.

To study the etiology of acute hepatitis superimposed upon previously unrecognized asymptomatic HBsAg carriers, paired sera were collected in acute and convalescence phases for measurement of HBeAg, anti-HBe, hepatitis B virus DNA and anti-delta from 76 adult patients with acute hepatitis who were HBsAg positive but IgM anti-HBc negative or positive only at low titer. None of them were IgM anti-hepatitis A virus positive on admission. Of the 34 patients who were HBeAg positive initially, two (5.9%) were diagnosed as having delta superinfection, and another two (5.9%) were suspected to have non-A, non-B virus superinfection because of a transient decrease of serum hepatitis B virus DNA. The remaining 30 (88.2%) cases were hepatitis B virus DNA negative with or without anti-HBe seroconversion on follow-up. The episodes of acute hepatitis in these cases may represent "immune clearance of HBeAg" or "immune clearance of hepatitis B virus with delayed anti-HBe seroconversion," respectively, in the natural course of chronic hepatitis B virus infection. Of the patients who were anti-HBe positive initially, 23 (54.8%) were diagnosed as having delta superinfection, including eight with de novo seroconversion of anti-delta and 15 with a rising titer of anti-delta; 10 (23.8%) were positive for hepatitis B virus DNA and were considered as reactivation of hepatitis B virus, and the other nine (21.4%) were suspected as having non-A, non-B virus superinfection.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of IgM anti-HBc in the etiologic diagnosis of HBsAg-positive acute and chronic hepatitis.

HBsAg, HBeAg, anti-HBc, anti-HBs, IgM anti-HAV, total and IgM anti-delta (RIA) and IgM anti-HBc (ELISA) have been determined on sera of 72 male patients with acute hepatitis (68 HBsAg positive and 4 anti-HBc-positive) at the onset of the disease and at 2, 4 and 6 months thereafter, and of 77 patients with HBsAg-positive chronic active hepatitis. The results indicate that testing for IgM anti-HBc in acute hepatitis is necessary to identify cases of hepatitis B even in the absence of positivity for HBsAg and/or HBeAg. HBsAg-positive cases, negative for IgM anti-HBc, were due to delta superinfection of chronic carriers of HBsAg. Recovery was always associated with negativity of IgM anti-HBc; IgM anti-HBc persistence was not found in all cases evolved to chronicity. In chronic hepatitis cases positivity for IgM anti-HBc was found only in 39% of the anti-delta-negative and only in 5.5% of the anti-delta-positive cases.

Clinical and serological outcome of acute delta infection.

To assess the clinical and serological outcome of hepatitis delta virus (HDV) infection, 59 patients with acute delta hepatitis were followed for 6-28 months. Forty-two patients had simultaneous HDV and HBV coinfection (anti-HBc IgM-positive, group I) and 17 were HBsAg carriers with HDV superinfection (anti-HBc IgM-negative, group II). Overall, serum HD-Ag and anti-HD IgM were the most sensitive markers for diagnosis of delta infection during the first 2 weeks after onset of symptoms. The clinical presentation was similar in both groups; 4 patients (1 in group I and 3 in group II) (7%) developed fulminant hepatitis, but none of them died. The majority of patients with HBV-HDV coinfection (group I) eventually recovered, whereas all HBsAg carriers with HDV superinfection (group II) developed chronic liver disease. Liver histology in these patients showed chronic active hepatitis and/or cirrhosis in 90%. The hepatic lesion was probably due to persistent HDV infection, as indicated by the presence of intrahepatic HD-Ag and/or persistence of serum anti-HD IgM in 90% of the patients.

Etiology of sporadic acute viral hepatitis in Taiwan: the role of hepatitis C virus, hepatitis E virus and GB virus-C/hepatitis G virus in an endemic area of hepatitis A and B.

The etiology of sporadic acute hepatitis was studied in 334 consecutive patients from Taiwan (237 men and 97 women, aged 16-81 years), with emphasis on the role of hepatitis C virus (HCV), hepatitis E virus (HEV), and GB virus-C/hepatitis G virus (GBV-C/HGV) in acute non-A, non-B (NANB) hepatitis and in HBsAg carriers with superimposed acute hepatitis. According to the conventional diagnostic criteria, there were 12 cases (3.6%) of acute hepatitis A, 17 cases (5.1%) of acute hepatitis B, 128 cases (38.3%) of acute NANB hepatitis, and 177 cases (53.0%) of acute hepatitis in HBsAg carriers (those who were HBsAg positive but IgM anti-HBc negative). Among 128 cases of acute NANB hepatitis, 70 (54.7%) had acute hepatitis C (HCV RNA positive), 5 (3.9%) had acute hepatitis E (IgM anti-HEV positive), and the other 53 (41.4%) were presumably acute hepatitis non-A-E. The prevalence of acute hepatitis A, B, E, and non-A-E showed no significant sex difference, whereas acute hepatitis C was significantly more prevalent in females. The prevalence of acute hepatitis A and B decreased and that of acute hepatitis C increased significantly with increasing age. In contrast, acute hepatitis E and non-A-E showed no significant age predominance. Of 177 HBsAg carriers with acute hepatitis, 64 (36.1%) demonstrated non-B hepatotropic virus superinfection, with HCV being the most common (60.9%), followed by hepatitis D, E, and A viruses, and the other 55 (31.1%) and 58 (32.8%) were presumed to have acute exacerbation of chronic hepatitis B or superimposed acute hepatitis non-A-E, respectively. Serum GBV-C/HGV RNA was detected in 3-4% of acute hepatitis non-A-E cases, suggesting its limited role in these cases.

[The etiological structure of acute viral hepatitis in Tadzhikistan in a period of decreased morbidity].

In the period of reduced incidence of viral hepatitis in Tajikistan, January-December, 1990, 1562 patients with acute viral hepatitis (AVH) were examined in the first days of the jaundice phase (928 children under 14 years and 634 adults) in Dushanbe. Markers of hepatitis A, B, and D (HBsAg, anti-HA IgM, anti-HBc IgM, anti-delta IgM) were determined by enzyme immunoassay. Hepatitis A occurred in 25.8% of the patients with AVH, mostly children of 1-6 years, HB in 22.8%, HD co- and superinfection) in 9.2%. In 42.1% of the patients who had no HA, HB, or HD markers in the blood, non-A, non-B hepatitis (mostly hepatitis E) was diagnosed, mainly in the age groups of 30-39 years (70.7%) and 15-29 years (59.2%). Thus, in Tajikistan hepatitis E occurs not only during outbreaks of this infection but also sporadically.

Etiology of fulminant viral hepatitis in Greece.

The etiology of fulminant viral hepatitis was determined in 65 consecutive cases among 1,814 (3.58%) adults with acute viral hepatitis who were admitted to the Infectious Diseases Hospital of Athens from May, 1981 to August, 1983. Radioimmunoassays were used to detect hepatitis B virus, hepatitis A virus and delta-agent markers. Enzyme immunoassay was used to detect anti-HBc IgM. Hepatitis B virus was responsible for 48 (73.9%), non-A, non-B for 16 (24.6%) and hepatitis A virus for one case (1.5%). The use of anti-HBc IgM identified 10 cases of fulminant type B hepatitis among HBsAg negative, anti-HBc and anti-HBs positive patients. Fulminant non-A, non-B hepatitis was superimposed on 10 asymptomatic HBsAg carriers; delta-agent co-infection was diagnosed in two fulminant type B hepatitis cases. These data show that hepatitis B virus is the major cause of fulminant hepatitis in Greece. HBsAg carriers are at high risk for fulminant non-A, non-B hepatitis. delta-agent does not seem to be as important as in Italy and other countries.

Hepatitis A and non-A, non-B viral hepatitis in São Paulo, Brazil: epidemiological, clinical and laboratory comparisons in hospitalized patients.

During a 33-month period, 295 patients with acute viral hepatitis were admitted to a state hospital for civil servants and their dependents in São Paulo, Brazil. Seventy-nine per cent (232) were HBsAg negative. To define the contribution of non-A, non-B viral hepatitis to hepatitis morbidity in this population, further serological studies were performed in 147 confirmed HBsAg-negative patients. One hundred and twelve (76%) were serologically classified as hepatitis A based on identification of IgM antibody to hepatitis A virus. Thirty patients (20%) without IgM antibody to hepatitis A virus, HBsAg, or anti-HBc were categorized as the non-A, non-B hepatitis group. The remaining five patients had probable hepatitis B (IgM antibody to hepatitis A virus negative, HBsAg negative, anti-HBs negative but anti-HBc positive). These data suggest that all three etiological forms of viral hepatitis are endemic in São Paulo. Epidemiological, clinical, and laboratory features were compared to the hepatitis A and non-A, non-B hepatitis groups. Patients with non-A, non-B hepatitis were significantly older than patients with hepatitis  A (mean age +/- S.D.: 30 +/- 22 years vs. 9 +/- 9 years, p less than 0.001). Contact with hepatitis or jaundice was recognized in 26 (23%) of 112 hepatitis A patients and 3 (10%) of 30 non-A, non-B patients, a difference which was not statistically significant. Parenteral exposures were identified in 13 (43%) of 30 patients with non-A, non-B hepatitis and 23 (21%) of the 112 hepatitis A patients. Blood transfusion in the 2 months preceding onset of illness was reported in 5 (17%) of the 30 non-A, non-B patients and in none of the hepatitis A group (p less than 0.001). Although prodromal symptoms and fever were more common in patients with hepatitis A, neither these nor other clinical features appeared to be distinguishing characteristics. Similarly, mean peak SGPT levels, peak SGPT levels of greater than or equal to 1,000 IU/per liter, and the mean duration of SGPT elevations for each group were not significantly different. Mean peak serum bilirubin levels were slightly higher in the non-A, non-B group than in the hepatitis A group (7.6 +/- 8.0 mg per dl vs. 5.1 +/- 2.7, p less than 0.01) and peak bilirubin levels greater than or equal to 10 mg per dl were found in 27% of the non-A, non-B group and 5% of the hepatitis A group (p less than 0.001). Whether the higher bilirubin levels reflect an agent-related phenomenon or an older population of affected patients is uncertain.

Fulminant viral hepatitis: Indian experience.

Thirty-six patients with fulminant viral hepatitis were studied. Enzyme immunoassay was used to detect the presence of HBsAg, IgM anti-HBc, and IgM anti-HAV. Non-A, non-B virus was the most common aetiological agent (61.1%) followed by hepatitis B virus (HBV; 30.6%) and hepatitis A virus (8.3%). Presence of IgM anti-HBc confirmed the diagnosis of HBV infection in three cases who were negative for HBsAg. Similarly, in one case who was positive for HBsAg, absence of IgM anti-HBc suggested superinfection with some other agent. Survival was significantly higher (P less than 0.01) in the hepatitis A virus (HAV) group (66.6%) compared with non-A, non-B (31.2%) and HBV groups (27.3%). Fever at the onset of illness was seen in all patients with HAV, 54.5% of patients with HBV and 38.88% of patients with non-A, non-B infection (P less than 0.01). The median time interval between the first symptom and the onset of encephalopathy was 16, 13 and 8 days in HAV, HBV and non-A, non-B groups, respectively, but this difference was statistically not significant (P greater than 0.05).

Serological diagnosis of jaundice epidemics in India.

Enterically transmitted non-A, nonB- hepatitis (ET-NANBH) is a major public health problem in India, where the endemicity of this disease is high and poor public sanitation coupled with compromised quality of drinking water leads to major and minor outbreaks. Sophisticated technics for characterization of hepatitis E virus (HEV) are not easily available/affordable, resulting in continuation of the diagnosis of NANBH for most epidemics. This study attempts to serologically determine the etiology of epidemics of NANBH in India. Eighteen outbreaks of jaundice occurring in various regions of India over a period of twenty months were selected for this laboratory based study. Representative cases of each outbreak were subjected to detailed serological investigation for immunological markers of viral hepatitis. Each serum sample was tested for the immunological markers of acute or recent infection with hepatitis A or B viruses (anti-HAV-IgM, HBsAg and anti-HBc-IgM) by Macro ELISA (Abbott). The sera found to be negative for these three markers ie non-A, non-B hepatitis (NANBH) sera were further tested for anti-HEV by Macro ELISA (anti-HEV EIA, Abbott). A highly significant number of NANBH sera were reactive for anti-HEV in case of almost all the outbreaks. The lowest figure for anti-HEV positivity in NANBH sera of outbreak was compared with anti-HEV positivity in the controls and found to be significantly high. It was concluded that anti-HEV is an important marker revealing probability of the NANBH outbreak being due to HEV.

Seroconversion

On a serological assay, the presence of hepatitis B surface antigen (HBsAg) indicates an individual with a currently active hepatitis B infection, whether acute or chronic. The presence of core antibody (anti-HBc) indicates an individual with an infection in general, whether current or previously resolved. The presence of surface antibody (anti-HBs) indicates an individual with immunity to hepatitis B, whether due to previously resolved infection or due to hepatitis B vaccination. For example, an individual who has never had any exposure to HBV, either by vaccine or by infection, would test negative for the entire serology panel. An individual who has been vaccinated and never had an infection will test seropositive for anti-HBs due to vaccination and negative for markers of infection. An individual with an acute HBV infection would test positive for HBsAg and anti-HBc (total and IgM) while negative for anti-HBs. An individual with a chronic infection would test positive for HBsAg and

Active surveillance for acute viral hepatitis in rural villages in the Nile Delta.

Acute viral hepatitis is less frequent in Egypt than serum antibody levels suggest. Because acute viral hepatitis has a wide clinical spectrum, we tested the hypothesis that many cases are undetected because of mild illness caused by initial, early-childhood exposure to hepatitis viruses. During active case detection among 20,000 inhabitants of rural villages in Egypt, we screened 1715 symptomatic patients for serum alanine aminotransferase (ALT) levels. Viral hepatitis markers were tested in 47 subjects who had ALT levels that were least twice the normal level. Of the 47 individuals tested, 4 children aged 3-5 years had immunoglobulin M (IgM) antibodies to hepatitis A virus (anti-HAV IgM). One also had a possible false-positive result to a test for IgM antibodies to hepatitis E virus. None had serological evidence of acute hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection. However, 33 of the remaining 43 had active HCV infection, having both antibodies to HCV (anti-HCV) and HCV RNA. Four others anti-HCV without HCV RNA, and 2 others had seroconversion to anti-HCV during follow-up. Two patients who were positive for hepatitis B surface antigen had chronic HBV infection. Only 3 with elevated ALT levels had no evidence of acute or chronic infections with known hepatitis viruses. Immunoglobulin G antibodies to hepatitis E virus was detected in 40 patients. Active surveillance covering approximately 50,000 person-years detected only 4 cases of acute HAV infection. Almost all persons with mild symptoms and elevated ALT levels had serological evidence of chronic viral hepatitis, most often associated with HCV. Many of these cases were probably "flare-ups" of HCV infection or incidental illness in patients with chronic HCV infection, but some could have been caused by difficult-to-confirm initial HCV infections. Although serological evidence for exposures was highly prevalent, hepatitis viruses seldom caused acute viral hepatitis in these communities.

Non-A, non-B viral hepatitis in Egypt.

A study was carried out on 200 patients of ages 20-40 years suffering from acute viral hepatitis. Sera were tested for markers of hepatitis B (HBsAg, and IgM anti-HBc) and hepatitis A (IgM-anti-HAV) by the ELISA technique. Sera negative for the markers of both viruses: Hepatitis A (HAV) and Hepatitis B (HBV) were subsequently tested for IGM Heterophil antibodies against Epstein-Barr virus (EBV) by the Monospot slide test to diagnose acute infectious mononucleosis and tested for anti-CMV (IgM) by ELISA technique for the diagnosis of acute Cytomegalovirus (CMV) infection. Non-A, non-B hepatitis (NANB) was diagnosed by exclusion. The results of the study showed that 133 (66.5%) patients had evidence of HBV infection, while only 9(4.5%) were diagnosed as HAV infection. EBV and CMV were the possible etiological agents of acute viral hepatitis in (3.5%) and 1%) respectively. Accordingly the Non-A, non-B hepatitis in this study amounts to (24.5%) of the acute viral hepatitis.

Vaccine-induced seropositivity

Hepatitis B When a person gets a hepatitis B vaccine then the most common test for hepatitis B will show them to be positive. The usual course of action, in this case, is to give the person a panel of tests for HBsAg, anti-HBc, and anti-HBs (hepatitis B surface antigen, anti-hepatitis B core, and anti-hepatitis B surface). A person who has never been exposed to hepatitis B but has gotten the vaccine will be positive for anti-HBs but negative for the other two tests in the panel. Other combinations of positive and negative in this test can mean other things, such as acute, chronic, or past infection.

Hepatitis

Viral hepatitis Viral hepatitis is primarily diagnosed through blood tests for levels of viral antigens (such as the hepatitis B surface or core antigen), anti-viral antibodies (such as the anti-hepatitis B surface antibody or anti-hepatitis A antibody), or viral DNA/RNA. In early infection (i.e. within 1 week), IgM antibodies are found in the blood. In late infection and after recovery, IgG antibodies are present and remain in the body for up to years. Therefore, when a patient is positive for IgG antibody but negative for IgM antibody, he is considered immune from the virus via either prior infection and recovery or prior vaccination. In the case of hepatitis B, blood tests exist for multiple virus antigens (which are different components of the virion particle) and antibodies. The combination of antigen and antibody positivity can provide information about the stage of infection (acute or chronic), the degree of viral replication, and the infectivity of the virus.

Needlestick injury

Treatment After a needlestick injury, certain procedures can minimize the risk of infection. Lab tests of the recipient should be obtained for baseline studies, including HIV, acute hepatitis panel (HAV IgM, HBsAg, HB core IgM, HCV) and for immunized individuals, HB surface antibody. Unless already known, the infectious status of the source needs to be determined. Unless the source is known to be negative for HBV, HCV, and HIV, post-exposure prophylaxis (PEP) should be initiated, ideally within one hour of the injury. Hepatitis B The risk of hepatitis B (e antigen positive) seroconversion is estimated at 37–62%, significantly more than other blood borne pathogens. After exposure to the hepatitis B virus (HBV), appropriate and timely prophylaxis can prevent infection and subsequent development of chronic infection or liver disease. The mainstay of PEP is the hepatitis B vaccine; in certain circumstances, hepatitis B immunoglobulin is recommended for added protection.

Delta infection and hepatitis B virus replication in Danish patients with fulminant hepatitis B.

The presence of hepatitis B virus and delta agent markers was investigated in 41 patients referred during the years 1970-1985 with fulminant hepatitis classified as type B or non-A non-B and compared to findings in patients with uncomplicated hepatitis B and chronic hepatitis B infection. 13 patients had no markers of hepatitis B and delta infection and were classified as non-A non-B hepatitis. The remaining 28 patients were all HBsAg and IgM anti-HBc positive and 14 (50%) had evidence of delta infection. In contrast, only 13/71 patients (18%) with acute benign hepatitis B had evidence of delta coinfection (p less than 0.005). This corresponds to an odds ratio of 4.5 for development of fulminant hepatitis among patients with hepatitis B and delta coinfection. In 100 chronic HBsAg carriers 29% were positive for delta markers. 12 of the delta infected patients with fulminant hepatitis were positive for total antibody to the delta antigen, and 2 were delta antigen positive. Three were HBeAg positive/anti-HBe negative. None had hepatitis B virus DNA. Among the 14 patients without delta infection, hepatitis B virus DNA was found in 2/4 HBeAg positive/anti-HBe negative patients and in 1/8 patients negative for both markers. The present data indicate that a high proportion of Danish patients with fulminant hepatitis B have hepatitis B and delta agent coinfection. Further, the findings suggest that hepatitis B and delta coinfection may be associated with an increased risk of development of fulminant hepatitis as compared to that of hepatitis B alone.

Differential diagnosis of acute HBsAg positive hepatitis using IgM anti-HBc by a rapid, fully automated microparticle enzyme immunoassay.

We determined the diagnostic significance of IgM anti-HBc by a rapid, fully automated microparticle enzyme immunoassay (IMx CORE-M) in acute HBsAg positive hepatitis. We studied prospectively for at least 6 months 100 patients with acute self-limited hepatitis B (group A) and 40 patients with acute hepatitis superimposed on histologically confirmed chronic hepatitis B (group B). On admission, all patients in group A were positive and those in group B were negative for IgM anti-HBc by a commercially available enzyme immunoassay. Based on the assay criteria, the rates of IMx CORE-M (> 1.2) positive serum samples on admission, 4, 12 and 24 weeks later were: in group A: 100%, 95%, 72%, 44% and in group B: 20%, 27.5%, 17.5%, and 15%, respectively. Misclassification was observed in 20-27.5% of the acute on chronic hepatitis B cases. However, the mean IMx CORE-M index value was found to be significantly higher in group A during the whole follow-up. In particular, on admission the mean IMx CORE-M index value was 2.504 +/- 0.435 (range: 1.508-3.482) in group A and 0.747 +/- 0.346 (range: 0.062-1.384) in group B (p < 0.001). Discriminant function analysis showed that the cutoff level between the two groups for IMxCORE-M index on admission was 1.5. Four to 12 weeks from admission, in the group with acute on chronic hepatitis B cases, 13 patients with HDV and/or HCV superinfection had significantly lower IMx-CORE M index values compared with 27 patients with acute hepatitis due to exacerbation of chronic hepatitis B. IMx CORE-M appears to be an accurate diagnostic test to differentiate acute from acute on chronic HBsAg positive hepatitis, but the cut-off level seems to be higher (1.5 instead of 1.2).

Acute liver failure

Initial laboratory analysis Prothrombin time/INR Complete blood count Chemistries Liver function test: AST, ALT, alkaline phosphatase, GGT, total bilirubin, albumin Creatinine, urea/blood urea nitrogen, sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate Glucose Amylase and lipase Arterial blood gas, lactate Blood type and screen Paracetamol (acetaminophen) level, toxicology screen Viral hepatitis serologies: anti-HAV IgM, HBSAg, anti-HBc IgM, anti-HCV Autoimmune markers: ANA, ASMA, LKMA, immunoglobulin levels Ceruloplasmin level (when Wilson's disease suspected) Pregnancy test (females) Ammonia (arterial if possible) HIV status (has implication for transplantation) History taking should include a careful review of possible exposures to viral infection and drugs or other toxins. From history and clinical examination, the possibility of underlying chronic disease should be ruled out as it may require different management.

[Changes in the response time of anti-HBc IgM in a hepatitis B case load. Diagnostic implications].

Anti-HBc IgM were determined in 46 patients whose serum was positive for hepatitis B surface antigen (HBsAg). All sera were tested from 1:4000 up to 1:8128000 dilution with a radioimmunometric assay. Anti-HBc IgM persisted at detectable level for up 15 months from acute infection in more than 50% of the patients. High levels of anti-HBc IgM are seen only in the acute phase but it is difficult to establish a cut-off dilution displaying diagnostic value between current and remote infection. Anti-HBc IgM are always detectable in acute hepatitis B virus (HBV) so that the absence of HBc IgM in acute hepatitis with positive HBsAg allows to discard HBV as the causative agent and to suspect a non-B hepatitis (A, delta, NANB). On the contrary the presence of anti-HBc IgM in detectable amounts in patients with acute hepatitis and negative HBsAg makes possible the diagnosis of acute B virus hepatitis.

Window period

Hepatitis B Two periods may be referred to as window period in hepatitis B infection: (1) the period that elapses during HBsAg to HBsAb seroconversion, i.e. between the disappearance of surface antigen (HBsAg) from serum and the appearance of HBsAb (anti-HBs), and (2) the period between infection and appearance of HBsAg. During the window of HBsAg to HBsAb seroconversion, IgM anti-core (HBc-IgM) is the only detectable antibody. HBV DNA may be positive as well. This window period does not occur in persons who develop chronic hepatitis B, i.e. who continue to have detectable HBV DNA for greater than 6 months (HbsAg remains positive), or in people who develop isolated HBcAb positivity, i.e. who lose HBsAg, but do not develop HBsAb (HBV DNA may or may not remain positive). See also Incubation period, the time between infection and the appearance of symptoms References HIV/AIDS Serology

List of hepato-biliary diseases

Hepato-biliary diseases include liver diseases and biliary diseases. Their study is known as hepatology. Liver diseases Viral hepatitis Acute hepatitis A Acute hepatitis B Acute hepatitis C Acute hepatitis D – this is a superinfection with the delta-agent in a patient already infected with hepatitis B Acute hepatitis E Chronic viral hepatitis Other viral hepatitis viruses may exist but their relation to the disease is not firmly established like the previous ones (hepatitis F, GB virus C, hepatitis X) Other infectious diseases Hepatitis: cytomegalovirus infection herpesviral: herpes simplex infection Toxoplasmosis Hepatosplenic schistosomiasis Portal hypertension in schistosomiasis Liver disease in syphilis Epstein–Barr virus infection yellow fever virus infection rubella virus infection leptospirosis Echinococcosis Amoebiasis

InternalMed_Harrison

Serologic Tests of Patient’s Serum Note: See text for abbreviations. the absence of HBsAg when IgM anti-HBc is detectable. A diagnosis of acute hepatitis A is based on the presence of IgM anti-HAV. If IgM anti-HAV coexists with HBsAg, a diagnosis of simultaneous HAV and HBV infections can be made; if IgM anti-HBc (with or without HBsAg) is detectable, the patient has simultaneous acute hepatitis A and B, and if IgM anti-HBc is undetectable, the patient has acute hepatitis A superimposed on chronic HBV infection. The presence of anti-HCV supports a diagnosis of acute hepatitis C. Occasionally, testing for HCV RNA or repeat anti-HCV testing later during the illness is necessary to establish the diagnosis. Absence of all serologic markers is consistent with a diagnosis of “non-A, non-B, non-C” hepatitis, if the epidemiologic setting is appropriate.

Diagnostic significance of IgM antibody to hepatitis delta virus in fulminant hepatitis B.

The prevalence of hepatitis delta virus (HDV) infection was studied in 25 adult patients with fulminant hepatitis who were admitted consecutively to our unit from February, 1986, to September, 1988. Enzyme and radioimmunoassays were used for the detection of serological markers of HAV, HBV, and HDV (HDAg, IgM anti-HD, total [IgG] anti-HD) infections. Two hundred twenty-nine serum samples (three to 19 samples/patient) were tested for serological markers of HDV infection. Of the 25 patients, 17 (68%) were HBsAg-positive, and the remaining eight (32%) were HBsAg-negative on admission to the hospital. All patients were seropositive for IgM anti-HBc. Serological markers of HDV infection were detected in 13 (52%) of the 25 patients. In particular, HDV infection was observed in nine (53%) of the 17 HBsAg-positive and in four (50%) of the eight HBsAg-negative patients with type B fulminant hepatitis. Survival was 16.7% for patients with hepatitis B and 57.8% for patients with B and D coinfection. Coinfections were responsible for fulminant hepatitis in 100% of drug addicts and 40% in patients who were not drug addicts. All patients with HBV/HDV coinfections became seropositive for IgM anti-HD. The results show that HDV infection has a significant role (52%) in type B fulminant hepatitis in an area with a moderate prevalence of HBV infections, that it should be tested in cases with early clearance of HBsAg, and that it does not seem to be accompanied by a high fatality rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Absence of circulating HBsAg in acute hepatitis B.

We are describing five of a group of 72 cases of acute hepatitis B in which HBsAg was not present when the disease was diagnosed, i.e. two to six days after the appearance of icterus. The role of HBV infection was assessed by demonstrating the absence of anti-HBs during the first few weeks and its appearance at the time of recovery, as well as the presence of anti-HBe, high anti-HBc titers and the IgM class of immunoglobulin. The high levels of transaminases observed in early sera returned to normal values within two to six weeks. Anti-HAV antibodies were absent in all serum samples tested. These case reports should remind us that the absence of HBsAg at the onset of acute viral hepatitis does not exclude the possibility of HBV infection. Therefore, if HBsAg and anti-HAV are not present at the beginning of acute viral hepatitis, serum should also be tested for anti-HBc IgM before the diagnosis of non-A, non-B hepatitis is considered.

Hepatitis B -- Evaluation -- Interpretation of Serologic Markers

Following serologic markers are often tested: Hepatitis B surface antigen (HBsAg), antibody to Hepatitis B surface antigen (anti-HBs), Hepatitis B core Ab (Anti-HBc) IgM, Hepatitis B core Ab (Anti-HBc) IgG, Hepatitis B e antigen (HBeAg), and Hepatitis B e antibody (anti-HBe). [10] HBsAg: Acute infection (less than 6 months) or chronic infection (more than 6 months). Anti-HBs: Recovery from acute infection or immunity from vaccination. HBeAg: Mostly associated with high viral load. Anti-HBe: Low replicative phase. Anti-HBc IgM: Acute infection, an only marker present in the window period, can be present during exacerbation of chronic infection. Anti-HBc IgG: Exposure to infection, chronic infection (if present along with HBsAg), recovery from acute infection (if present with anti-HBs), if isolated presence, may represent occult infection.

Acute non-A, non-B hepatitis in Kuwait.

In a prospective study of acute hepatitis in Kuwait covering the period February 1983 to January 1984, a total of 1781 cases were diagnosed as having an acute viral hepatitis. 1,384 (77.7%) were found to be due to hepatitis A virus (HAV), 206 (11.5%) hepatitis B virus (HBV), 8 (0.4%) coinfection with HBV and delta virus (HDV), 8 (0.4%) superinfection of HDV on chronic HBsAg carriers and 157 (9%) non-A, non-B virus (NANB). 13 cases of CMV and 5 of EBV infections were also diagnosed. NANB viral hepatitis was a disease of young adults (mean age 29 years) with a male-female ratio of 3:1. A high incidence was noted among males from the Indian subcontinent (29.1/100,000 of population, compared to 5.4/100,000 among local Arabs), the majority of whom gave a history of recent visit to the Indian subcontinent. The clinical features and biochemical findings of acute NANB infection were found to be less severe than those of acute HBV infection and similar to acute HAV infection. Three patients (2.3%) with acute NANB virus infection developed chronic hepatitis (all women), and another 3 patients died because of fulminant hepatitis.

[Hematological abnormalities in acute viral hepatitis and acute hepatitis in HBsAg carrier].

Various kinds of hematological abnormalities have been known to occur in liver diseases. To understand the hematological changes in acute viral hepatitis, 324 adults with acute viral hepatitis were studied. Of them, 3 were acute hepatitis A, 91 acute hepatitis B, 99 acute non-A, non-B hepatitis (NANB) and 181 acute hepatitis on chronic hepatitis B (AH on CH-B). There were 233 males and 91 females; age ranged from 16 to 74 years (mean age 39 years.) The results showed the incidences of thrombocytopenia (platelet less than 120,000/cmm), anemia (Hb less than 12 g% in male and less than 10% in female patients), leukocytosis (WBC greater than 10,000/cmm) and leukopenia (WBC less than 4,000/cmm) were 19.3%, 12.6%, 10.8% and 7.4%, respectively. Patients with AH on CH-B had significantly higher incidence of anemia and thrombocytopenia than those with acute B hepatitis; other than this, there was no significant difference. Patients with anemia, thrombocytopenia or leukocytosis had significantly higher mean levels of serum bilirubin and higher proportions of prolonged prothrombin time, suggesting that these hematological abnormalities were closely related to the severity of hepatocellular damage. In addition, there were 3 cases (0.9%) complicated with aplastic anemia. Two were NANB hepatitis and the other was AH on CH-B which was seronegative for anti-delta, possibly suggesting NANB virus superinfection. Of these 3 cases, 2 died of complications related to aplastic anemia and 1 survived with normal hematological findings 148 days later.

SEROPREVALENCE OF HAV, HBV, HCV, AND HEV AMONG ACUTE HEPATITIS PATIENTS AT KENYATTA NATIONAL HOSPITAL IN NAIROBI, KENYA.

Acute viral hepatitis is most frequently caused by the hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV). To determine seroprevalence of HAV, HBV, HCV and HEV among patients with acute hepatitis in Nairobi, Kenya, elucidate various risk factors for hepatitis viral infection and determine the co-infection rates with these viruses in the acute hepatitis patients. Across sectional descriptive study. Kenyatta National Hospital, from November 2007 to April 2008. One hundred patients were recruited by purposive sampling method and comprised of 57 males and 43 females. Among the enrolled patients, twenty three tested positive for one or more markers of acute viral hepatitis, that is, HAV, HBV, HCV and HEV. No markers were detected in 77patients, 2% tested positive for IgM anti-HAV 11% for IgM anti-HBc; 3% for HBsAg; 5% for HCV RNA and 7% for IgM anti-HEV.Various risk factors associated with acute viral hepatitis were identified; poor sanitation, source of water, occupation, place of residence, level of education, household size, drug abuse and sexual behaviours. Co-infection rate with hepatitis Viruses was at 4%, IgM anti-HAV and IgM anti-HEV 1% (n=1); IgM anti-HBc and IgM anti-HEV 1% (n=1); IgM anti-HBc and anti-HCV 2% (n=2). Three patients were positive for HBsAg; among this two were negative for IgM anti-HBc and this accounted for HBV carriage (2%). Hepatitis viruses'infections are commoncause of hepatitis among patients with acute hepatitis at Kenyatta National Hospital. Co-infection with these viruses was also identified among these patients.