ABSTRACT
BACKGROUND: Although Hizentra is indicated for immunoglobulin replacement therapy in patients with primary and secondary immunodeficiencies, phase III trials have focused on patients with primary immunodeficiencies. In this 9-month, real-life, prospective, non-interventional, longitudinal, multicenter study of patients with primary and secondary immunodeficiencies in France, treatment modalities (primary endpoint), efficacy, safety, tolerability, quality of life, and treatment satisfaction were evaluated using descriptive statistics. RESULTS: Starting in January 2012, 117 patients were enrolled (99 adults, 18 children). Secondary immunodeficiencies were present in 48.7 % of patients. At follow-up, injections were administered every 7 days in 92.2 % of patients. Nine patients (7.8 %) were taking Hizentra every 10-14 days. The median dose of Hizentra administered was 0.1 g/kg/injection. Fifty-six patients were administered doses <0.1 g/kg/injection and 13 patients were administered doses >0.2 g/kg/injection. Mean trough IgG titers were 9.0 ± 3.3 g/L (median 8.3 g/L). The mean yearly rate of infection was 1.2 ± 1.9. Mean scores on the Short Form-36 physical and mental component summaries were 46.3 ± 10.0 and 46.6 ± 9.3, respectively. Scores on the Treatment Satisfaction Questionnaire for Medication ranged from 69.9 ± 19.9 to 88.3 ± 21.2 depending on the domain. Treatment with Hizentra was well tolerated. No single drug-related systemic reaction occurred in more than one patient and few local reactions were reported (n = 5). CONCLUSIONS: Under real-life conditions and in a cohort that included patients with primary and secondary immunodeficiencies, treatment with Hizentra was effective and well tolerated and patients were generally satisfied with the treatment.
ABSTRACT
More than 30 years after its individualization, chronic fatigue syndrome (CFS) remains a debilitating condition for the patient and a confusing one to the physicians, both because of diagnostic difficulties and poorly codified management. Despite the numerous work carried out, its pathophysiology remains unclear, but a multifactorial origin is suggested with triggering (infections) and maintenance (psychological) factors as well as the persistence of inflammatory (low grade inflammation, microglial activation ), immunologic (decrease of NK cells, abnormal cytokine production, reactivity to a variety of allergens, role of estrogens ) and muscular (mitochondrial dysfunction and failure of bioenergetic performance) abnormalities at the origin of multiple dysfunctions (endocrine, neuromuscular, cardiovascular, digestive ). The complexity of the problem and the sometimes contradictory results of available studies performed so far are at the origin of different pathophysiological and diagnostic concepts. Based on a rigorous analysis of scientific data, the new American concept of Systemic Disease Exertion Intolerance proposed in 2015 simplifies the diagnostic approach and breaks with the past and terminologies (CFS and myalgic encephalomyelitis). It is still too early to distinguish a new disease, but this initiative is a strong signal to intensify the recognition and management of patients with CFS and stimulate research.
Subject(s)
Fatigue Syndrome, Chronic/physiopathology , Diagnosis, Differential , Fatigue Syndrome, Chronic/diagnosis , HumansABSTRACT
BACKGROUND: IgG replacement therapy (IgRT) in primary immunodeficiencies (PID) is a lifelong treatment which may be administered intravenously (IVIg) or subcutaneously (SCIg), at hospital or at home. The objective of the VISAGE study was to investigate if route and/or place for IgRT impact patients' satisfaction regarding IgRT and quality of life (QoL) in real-life conditions. METHODS: The study enrolled PID patients at least 15 years old receiving IgRT for at least 3 months. Satisfaction and QoL were evaluated at enrollment and over a 12-month follow-up period by Life Quality Index (LQI) which measures 3 dimensions of satisfaction: treatment interference, therapy related problems and therapy settings (factors I, II and III) and SF-36 v2 questionnaire. RESULTS: The study included 116 PID patients (mean age 42 ± 18 years, 44 % males, 58 % with scholar or professional occupation) receiving IgRT for a mean of 8.5 ± 8.4 years. At enrollment they were receiving either home-based SCIg (51 %), hospital-based IVIg (40 %) or home-based IVIg (9 %). Patients exhibited a high degree of satisfaction regarding IgRT whatever the route and place for administration. LQI factor I was higher for home-based SCIg (86 ± 2) than for hospital-based IVIg (81 ± 3) and home-based IVIg (73 ± 5; p = 0.02 versus home-based SCIg); no difference was found for LQI factor II; LQI factor III was higher for home-based SCIg (92 ± 2) than for hospital-based IVIg (87 ± 5) and hospital-based IVIg (82 ± 3; p = 0.005 versus home-based SCIg). By contrast, every dimension of QoL was impaired. Over the follow-up period, 10 patients switched from hospital-based IVIg to home-based SCIg and improved LQI factor I (p = 0.004) and factor III (p = 0.02), while no change was noticed in LQI factors II and QoL. Meanwhile, no change in satisfaction or QoL was found in patients with stable route of IgRT. When asked on their preferred place of treatment all but one patient with home-based treatment would choose to be treated at home and 29 % of patients treated at hospital would prefer home-based IgRT. CONCLUSION: PID patients expressed a high degree of satisfaction regarding IgRT, contrasting with impaired QoL. In real-life conditions awareness of patient's expectations regarding the route or place of IgRT may be associated with further improvement of satisfaction.
Subject(s)
Immunoglobulins/therapeutic use , Immunologic Deficiency Syndromes/therapy , Quality of Life , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Immunotherapy , Male , Middle Aged , Patient Satisfaction , Personal Satisfaction , Surveys and Questionnaires , Young AdultABSTRACT
Iron deficiency anemia still remains problematic worldwide. Iron deficiency without anemia is often undiagnosed. We reviewed, in this study, symptoms and syndromes associated with iron deficiency with or without anemia: fatigue, cognitive functions, restless legs syndrome, hair loss, and chronic heart failure. Iron is absorbed through the digestive tract. Hepcidin and ferroportin are the main proteins of iron regulation. Pathogenic micro-organisms or intestinal dysbiosis are suspected to influence iron absorption.
Subject(s)
Intestinal Absorption , Intestinal Diseases/metabolism , Iron Deficiencies , Iron, Dietary/pharmacokinetics , Alopecia/etiology , Anemia, Iron-Deficiency/epidemiology , Anemia, Iron-Deficiency/etiology , Animals , Cation Transport Proteins/physiology , Cognition Disorders/etiology , Exercise Tolerance , Fatigue/etiology , Heart Failure/etiology , Humans , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/microbiology , Intestinal Diseases/complications , Intestinal Diseases/microbiology , Intestines/microbiology , Malabsorption Syndromes/complications , Mammals/metabolism , Microbiota , Restless Legs Syndrome/etiologyABSTRACT
Drug allergic reactions presenting as maculo-papular exanthema (MPE) are mediated by drug-specific T cells. In this study, the frequency of circulating specific T cells was analyzed by interferon-gamma (IFN-gamma) enzyme-linked immunospot assay in 22 patients with an allergic MPE to amoxicillin (amox). Amox-specific circulating T cells were detected in 20/22 patients with frequencies ranging from 1 : 8000 to 1 : 30 000 circulating leucocytes. No reactivity was observed in 46 control patients, including 15 patients with immunoglobulin E-mediated allergy to amoxicillin, 11 patients with a history of drug-induced MPE but tolerant to amoxicillin and 20 healthy individuals. Furthermore, amox-specific T cells were still detectable several years after the occurrence of the allergic reaction even after strict drug avoidance. Finally, analysis of drug-specific T cells in one patient allergic to ticarcillin (a penicillin antibiotic distinct from amox) revealed the presence of IFN-gamma-producing T cells reactive to ticarcillin and several other betalactam antibiotics, suggesting that the IFN-gamma ELISPOT assay is able to detect T cell cross-reactivity against chemically related drugs. These findings confirm that drug-induced MPE is associated with the presence of specific T cells in blood and further suggest that the IFN-gamma ELISPOT is a sensitive assay which could improve the diagnosis of betalactam allergy.
Subject(s)
Amoxicillin/immunology , Anti-Bacterial Agents/immunology , Drug Hypersensitivity/immunology , Penicillins/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Amoxicillin/adverse effects , Anti-Bacterial Agents/adverse effects , Child , Child, Preschool , Cross Reactions , Drug Hypersensitivity/etiology , Enzyme-Linked Immunosorbent Assay , Exanthema/chemically induced , Exanthema/immunology , Humans , Infant , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Penicillins/adverse effects , Skin Diseases/chemically induced , Skin Diseases/immunology , Skin Tests , T-Lymphocytes/metabolismABSTRACT
The objective of the present study was to investigate the maturation of immunoglobulin G (IgG) avidity after Toxoplasma gondii seroconversion during pregnancy and the factors that affect IgG avidity over time. The study used 309 serum samples from 117 women and a multiple linear mixed regression analysis to show the patterns of variation of IgG avidity throughout gestation. The IgG avidity ratios and the patterns of their evolution with time were quite diverse among the women and were statistically heterogeneous (P = 0.011); however, the trend was toward a statistically significant increase (P < 0.0001). On average, a 1.0167-fold increase was observed for each additional gestational week after the putative date of infection. At 12 weeks after putative infection (the expected IgG avidity maturation time), the mean avidity ratio was 16.6% (95% confidence interval, 15.4 to 17.9%). At all times, the avidity ratio remained significantly heterogeneous among the women (P < 0.05); for 95% of them, that ratio ranged from 7.8 to 35.3% at 12 weeks after putative infection. Maternal age at the putative time of infection did not influence the maturation of IgG avidity. However, on average, a 1.009-fold decrease (P = 0.03) in that avidity was observed for each additional week of gestational age before infection and a 1.03-fold increase (P = 0.0003) was observed for each additional week of delay to the onset of spiramycin treatment. The rate of increase in the avidity ratio was lower if infection occurred late in pregnancy and higher if the delay to treatment was long. This information cannot allow accurate determination of the delay since the time of infection. The present results provide support for interpretation of the assay and caution against overinterpretation.
Subject(s)
Antibodies, Protozoan/immunology , Antibody Affinity , Coccidiostats/therapeutic use , Immunoglobulin G/immunology , Pregnancy Complications, Parasitic/drug therapy , Spiramycin/therapeutic use , Toxoplasma/immunology , Toxoplasmosis/drug therapy , Animals , Female , Gestational Age , Humans , Pregnancy , Pregnancy Complications, Parasitic/immunology , Retrospective Studies , Toxoplasmosis/immunologyABSTRACT
Humoral immune response is essential for protection against invasive pneumococcal disease and this property is the basis of the polysaccharide-based anti-pneumococcal vaccines. Pneumococcal surface protein A (PspA), a cell-wall-associated surface protein, is a promising component for the next generation of pneumococcal vaccines. This PspA antigen has been shown to stimulate an antibody-based immunity. In the present study, we evaluated the capacity of PspA to stimulate CD4+ T cells which are needed for the correct development of a B cell based immune response in humans. Cellular immunity to PspA was evaluated by whole-blood culture with different pneumococcal antigens, followed by flow cytometric detection of activated CD4+CD25+ T cells. T cell-mediated immune responses to recombinant PspA proteins were assessed in acute-phase and convalescent blood from adults with invasive pneumococcal disease and in blood from healthy subjects. All cases had detectable antibodies against PspA on admission. We found that invasive pneumococcal disease induced transient T cell depletion but adaptive immune responses strengthened markedly during convalescence. The increased production of both interleukin (IL)-10 and interferon (IFN)-gamma during convalescence suggests that these cytokines may be involved in modulating antibody-based immunity to pneumococcal disease. We demonstrated that PspA is efficient at eliciting T cell immune responses and antibodies to PspA. This study broadens the applicability of recombinant PspA as potent pneumococcal antigen for vaccination against S. pneumoniae.
Subject(s)
Bacterial Proteins/immunology , CD4-Positive T-Lymphocytes/immunology , Pneumococcal Infections/immunology , Pneumococcal Vaccines/administration & dosage , Streptococcus pneumoniae , Adult , Antibodies, Bacterial/immunology , B-Lymphocytes/immunology , Case-Control Studies , Flow Cytometry , Humans , Interferon-gamma/immunology , Interleukin-10/immunology , Interleukin-4/immunology , Lymphocyte Activation , Statistics, Nonparametric , VaccinationABSTRACT
Protection against Toxoplasma gondii in infected patients is mainly attributed to cellular immunity. We here attempt to improve the characterization of the proteins that induce cellular immunity in naturally infected patients. Cellular immunity was evaluated by flow cytometry after 7 days of blood culture from 31 chronically T. gondii infected and 8 noninfected pregnant women, in the presence of soluble T. gondii antigen (ST-Ag) or fractionated proteins from ST-Ag, separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Blood cultures from infected patients with ST-Ag induced 39.5 +/- 12.7% of activated (CD25+) CD4+ T cells using flow cytometry. This contrasts with the absence of activated CD4+ T cells after either culture with PBS or in blood cultures from noninfected women. The protein fraction between 21 and 41.9 kD induced the highest response (14.7 +/- 10.0%). Blood samples from 20 infected and 5 uninfected women were cultured in presence of 12 protein subfractions of 2-208 kD. The highest frequencies of response among infected patients were seen with fractions (Fr) 26-31.9 kD (C.I. 85-100%) and Fr 32-36.9 kD (C.I. 77-100%). Although we note a good concordance between cellular and humoral response, Western blot analysis of ST-Ag does not completely predict the panel of proteins recognized by cellular immunity. Two-dimensional separation of the ST-Ag revealed more than 200 protein spots in these fractions. However, only two proteins in the 20-40 kD range induced a significant humoral response. Further studies are necessary to determine which proteins in the Fr 26-31.9 kD and 32-36.9 kD are superior immunogens for cellular responses.
Subject(s)
Antigens, Protozoan/blood , CD4-Positive T-Lymphocytes/immunology , Toxoplasma/immunology , Toxoplasmosis/immunology , Animals , Antibodies, Protozoan/immunology , Antigens, Protozoan/immunology , Blotting, Western/methods , Case-Control Studies , Electrophoresis, Gel, Two-Dimensional , Female , Flow Cytometry , Humans , Lymphocyte Activation , Pregnancy , Receptors, Interleukin-2/immunologyABSTRACT
The aim of this study was to determine the frequency of anergy to Toxoplasma gondii in congenitally infected newborns and immunocompetent infected individuals. Specific anergy to Toxoplasma has been reported previously, especially in cases of congenital toxoplasmosis. Whole blood from 592 immunocompetent patients with suspected toxoplasmosis was cultured in the presence of soluble Toxoplasma antigen for 7 days. Activated T lymphocytes were detected by flow cytometry. In patients over 1 year of age, the percentage of soluble Toxoplasma antigen-stimulated T cells expressing the interleukin-2 receptor CD25 was higher in infected patients than in uninfected subjects (40.0+/-18.3% vs. 1.8+/-2.0%, P<0.0001). No differences were detected between seroconverters, i.e. those with recent rises in IgM and IgG antibodies, and those with acquired or congenital toxoplasmosis. Similar results were observed when congenitally infected ( n=38) and uninfected ( n=89) children under 1 year of age were compared (17.6+/-9.2% vs. 3.0+/-4.9%, P<0.0001). The sensitivity and specificity values of CD25 detection for diagnosis of congenital toxoplasmosis in infants were 95% and 89%, respectively, at a threshold value of 7% above control culture. The results show that specific cellular immunity is detectable in virtually all Toxoplasma-infected patients, including newborns. Detection of CD25 constitutes a simple, sensitive and specific test for diagnosis of congenital toxoplasmosis.
Subject(s)
Toxoplasma/immunology , Toxoplasmosis, Congenital/immunology , Animals , Female , Flow Cytometry/methods , Humans , Immunity, Cellular , Immunocompetence , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Infant, Newborn , Middle Aged , Pregnancy , Receptors, Interleukin-2/analysis , Receptors, Interleukin-2/metabolism , Sensitivity and Specificity , Spiramycin/pharmacology , T-Lymphocytes/immunology , Toxoplasma/drug effects , Toxoplasmosis, Congenital/diagnosis , Toxoplasmosis, Congenital/drug therapyABSTRACT
The parasite Toxoplasma gondii can infect most mammals and birds, sometimes causing severe pathology. Primary infection during pregnancy can result in abortion or fetal defects. Host immunity, particularly cellular immunity towards antigenic peptides, can control infection, but an efficient vaccine is not yet available. We have evaluated T-cell responses to a crude soluble toxoplasma antigen (ST-Ag) and to five recombinant peptide antigens of cells in whole-blood cultures from 22 pregnant women with preexisting infections and from 7 pregnant negative controls. Cells from all infected patients but from none of the controls responded specifically to ST-Ag by expressing surface CD25 on culture. Responses to the recombinant antigens showed considerable variation between individuals. rGRA1 elicited a response in 16 of the 22 samples (73%), rSAG1 in 13, rGRA7 in 9, rGRA6-CT in 4, and rGRA6-NT in only 1. Most responding cells were CD4(+). Cells from infected subjects cultured with ST-Ag all released high levels of gamma interferon (IFN-gamma) into the culture supernatant (4,343 +/- 2,536 pg/ml). Cells from 12 patients released IFN-gamma after culture with rGRA1 (130 +/- 98 pg/ml), those from 10 patients released it after culture with rSAG1 (183 +/- 128 pg/ml), and those from 4 patients released it after culture with rGRA7 (324 +/- 374 pg/ml). Intensity of IFN-gamma production in response to the latter two recombinant antigens correlated with responses to ST-Ag (r = 0.61 and 0.53, respectively; P < 0.01). Interleukin-4 was always absent from supernatants of cells stimulated with toxoplasma antigens. The heterogeneity of human responses to individual recombinant toxoplasma antigens should be considered in the design of potential vaccines.
Subject(s)
Antigens, Protozoan/immunology , CD4-Positive T-Lymphocytes/immunology , Interferon-gamma/biosynthesis , Pregnancy Complications, Parasitic/immunology , Protozoan Proteins/immunology , Receptors, Interleukin-2/biosynthesis , Toxoplasmosis/immunology , Animals , Antibodies, Protozoan/blood , Antibodies, Protozoan/immunology , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/parasitology , Cell Line , Cells, Cultured , Chronic Disease , Female , Humans , Immunity, Cellular , Interleukin-4/biosynthesis , Mice , Pregnancy , Pregnancy Complications, Parasitic/blood , Recombinant Fusion Proteins/immunology , Toxoplasma/immunology , Toxoplasmosis/bloodABSTRACT
Chronic fatigue syndrome or benign myalgic encephalomyelitis has been extensively described and investigated. Although numerous immunological abnormalities have been linked with the syndrome, none have been found to be specific. This article describes the detection of delayed-type hypersensitive responses to certain common environmental antigens in almost fifty per cent of patients with this syndrome. Such hypersensitivity can be detected by the intradermal administration of antigens derived from commensal organisms like the yeast Candida albicans, and then monitoring for a systemic reaction over the following six to forty eight hours. This approach can be consolidated by performing lymphocyte activation tests in parallel and measuring in vitro T-cell activation by Candida albicans antigens by three-colour flow cytometry based on CD3, CD4 and either CD69 or CD25. Another useful parameter is the kinetics of neopterin excretion in the urine over the course of the skin test. The results showed that the intensity of the DTH response correlated with the number of T-cells activated in vitro. Various factors have been implicated in the fatigue of many patients, notably lack of sleep. However, it remains difficult to establish causality in either one direction or the other. This work is in the spirit of a multifactorial approach to the group of conditions referred to as "chronic fatigue syndrome".
Subject(s)
Fatigue Syndrome, Chronic/immunology , Hypersensitivity, Delayed/immunology , Lymphocyte Activation , Neopterin/urine , T-Lymphocyte Subsets/immunology , Adolescent , Adult , Aged , Antigens, CD/analysis , Antigens, Differentiation, T-Lymphocyte/analysis , Antigens, Fungal/immunology , CD3 Complex/analysis , CD4 Antigens/analysis , Candida albicans/immunology , Cells, Cultured/immunology , Environmental Exposure , Fatigue Syndrome, Chronic/urine , Female , Flow Cytometry , Humans , Intradermal Tests , Lectins, C-Type , Male , Middle Aged , Receptors, Interleukin-2/analysisABSTRACT
UNLABELLED: Although serological rebound is common in infants with congenital toxoplasmosis, clinical recommendations for management, in particular the need for additional treatment, vary. The goals of our retrospective cohort study in 133 consecutive children with congenital toxoplasmosis were to estimate the incidence and duration of the rebounds, identify predictive factors, assess the long-term risk of eye lesions and the need for treatment. We first estimated the incidence and duration of rebounds and identified predictive factors using an univariate analysis and a Cox model modified to include time-dependent variables. Two cohort studies were then conducted to compare the incidence density of secondary eye lesions in children who had a rebound versus no rebound, and among children who had a rebound after initial therapy, in those who received an additional course of treatment and in those who did not. Of the 133 children, 93 (70%) had at least one rebound during a mean follow-up of 95 months. Of those with one rebound diagnosed after initial treatment, 33 received an additional 3-month course of pyrimethamine/sulphadoxine and 48 were not treated. Intracranial calcification at birth was associated with an increased relative risk (RR) of rebound (RR = 2.601; P = 0.03), and treatment with pyrimethamine/sulphadoxine between 2 and 12 months of age with a decreased risk (RR = 0.3; P = 0.0845), whereas age of pregnancy at maternal infection, type of treatment during pregnancy and sex were not found to be predictive factors. There was no difference in incidence densities of secondary eye lesions in children without rebound (7/3,367 child-months) compared to those with at least one rebound (22/9,609 child-months) (RR = 1.10; 95% CI: 0.47-2.58), and, among the 81 children who had one rebound diagnosed after initial treatment, in those who received an additional course of treatment and in those who did not (RR = 0.72; 95% CI: 0.30-1.72). CONCLUSION: serological rebound is common in children with congenital toxoplasmosis but, due to the risk and constraints, an additional course of treatment and more ophthalmological surveillance than currently practiced do not seem warranted.
Subject(s)
Antibodies, Protozoan/blood , Toxoplasma/immunology , Toxoplasmosis, Congenital/epidemiology , Toxoplasmosis, Congenital/immunology , Animals , Child , Child, Preschool , Female , Follow-Up Studies , France/epidemiology , Humans , Immunoglobulin G/blood , Incidence , Infant , Infant, Newborn , Male , Predictive Value of Tests , Pregnancy , Proportional Hazards Models , Recurrence , Retrospective Studies , Risk Factors , Toxoplasmosis, Congenital/prevention & controlABSTRACT
Natural interferon-alpha producing cells (IPCs) are a newly characterized blood cell type, which is the major source of type I interferons in antiviral innate immune responses. The relationship between the number of circulating IPCs, HIV disease progression, and the occurrence of HIV-related complications was investigated. The study of 25 healthy donors and 54 HIV-infected subjects demonstrated a direct correlation between blood IPC number, interferon-alpha production, and clinical state of HIV-infected subjects. Asymptomatic long-term survivors had increased IPC number and function relative to uninfected controls and infected individuals with progressive disease. IPC numbers were markedly reduced in AIDS patients developing opportunistic infections and cancer. A negative correlation was found between the IPC number in the blood and the HIV viral load, suggesting that IPCs are important in controlling HIV replication. This study provides the first evidence that IPCs are being affected during the course of HIV infection and suggests that these cells can play a vital role in the protection against opportunistic pathogens and cancer. (Blood. 2001;98:906-912)
Subject(s)
HIV Infections/blood , Interferon Type I/metabolism , Leukocytes, Mononuclear/metabolism , AIDS-Related Opportunistic Infections/blood , AIDS-Related Opportunistic Infections/diagnosis , Adult , CD4 Lymphocyte Count , Case-Control Studies , Female , HIV Infections/diagnosis , HIV Long-Term Survivors , Humans , Integrin alphaXbeta2 , Leukocyte Count , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/pathology , Male , Middle Aged , Prognosis , Sarcoma, Kaposi/blood , Severity of Illness Index , Viral LoadABSTRACT
OBJECTIVES: Toxoplasmosis serology may become temporarily negative in children with congenital toxoplasmosis, leading to a risk of misdiagnosis and inadequate surveillance. The purpose of our work was to better understand the time course of toxoplasmosis serology which has not been studied specifically and to propose practical recommendations. PATIENTS AND METHODS: We conducted a prospective study in 217 children born with congenital toxoplasmosis between January 1988 and December 1997. Clinical, ophthalmological and serology data were collected every three months during their first year of life then every six months until three years of age and every year thereafter for all patients. Negative serology was defined as the absence of IgG at indirect immunofluorescence and ELISA (enzyme linked immunosorbent assay) and by the absence of IgM at ISAGA (immunosorbent agglutination assay). RESULTS: During the mean follow-up of 66 +/- 33 months (range 12-126 months), 33 children (15%) presented a period where the toxoplasmosis serology (ELISA and indirect immunofluorescence) was negative for a transient period reaching a mean 5 months. The dye test was performed in 25 of these children and was negative in 6 (24%). Among the negative conversions observed at routine testing, 73% occurred in children taking pyrimethamine/sulfadoxin therapy and the others occurred a mean 11.7 months after interruption of treatment. There was a positive association between maternal treatment and transient seronegativity in the cases where the maternal contamination had occurred during the first 2 trimesters of pregnancy. The serology became positive again in 30 of the 33 children (91%) and in 22 children there was a rebound. At last follow-up, the 3 other children still had negative serology (mean duration 35 months, range 3-62 months). CONCLUSION: Transient negative toxoplasmosis serology is a frequent phenomenon in children with congenital toxoplasmosis. Although the underlying pathophysiological mechanism remains unknown, it is crucial to avoid questioning the initial diagnosis of congenital toxoplasmosis and to continue regular routine monitoring.
Subject(s)
Diagnostic Errors , Toxoplasmosis, Congenital/diagnosis , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , False Negative Reactions , Female , Fluorescent Antibody Technique , Humans , Infant , Male , Prospective Studies , Serologic Tests , Toxoplasmosis, Congenital/immunologyABSTRACT
Chronic fatigue syndrome or benign myalgic encephalomyelitis has been extensively described and investigated. Although numerous immunological abnormalities have been linked with the syndrome, none have been found to be specific. This article describes the detection of delayed-type hypersensitive responses to certain common environmental antigens in almost fifty per cent of patients with this syndrome. Such hypersensitivity can be detected by the intradermal administration of antigens derived from commensal organisms like the yeast Candida albicans albicans, and then monitoring for a systemic reaction over the following six to forty-eight hours. This approach can be consolidated by performing lymphocyte activation tests in parallel and measuring in vitro T-cell activation by Candida albicans albicans antigens by three-colour flow cytometry based on CD3, CD4 and either CD69 or CD25. Another useful parameter is the kinetics of neopterin excretion in the urine over the course of the skin test. The results showed that the intensity of the DTH response correlated with the number of T-cells activated in vitro. Various factors have been implicated in the fatigue of many patients, notably lack of sleep. However, it remains difficult to establish causality in either one direction or the other. This work is in the spirit of a multifactorial approach to the group of conditions referred to as "chronic fatigue syndrome".
Subject(s)
Fatigue Syndrome, Chronic/immunology , Flow Cytometry , Hypersensitivity, Delayed/immunology , Lymphocyte Activation , Neopterin/urine , T-Lymphocyte Subsets/immunology , Adolescent , Adult , Aged , Diagnosis, Differential , Fatigue Syndrome, Chronic/diagnosis , Fatigue Syndrome, Chronic/urine , Female , Hepatitis, Autoimmune/diagnosis , Humans , Hypersensitivity, Delayed/urine , Immunophenotyping , Magnesium Deficiency/diagnosis , Male , Middle Aged , Predictive Value of Tests , Sensitivity and Specificity , Severity of Illness Index , Spondylitis, Ankylosing/diagnosis , Surveys and QuestionnairesABSTRACT
Delayed type hypersensitivity (DTH) to Candida albicans is commonly observed in human. Abnormal DTH has already been described but its diagnosis is difficult to ascertain. We present now a clinical and biological study in 60 patients with a clear distinction between these two kind of Candida albicans DTH. Clinical abnormal Candida albicans DTH was characterized by a syndromic reaction 24 to 48 hours after intradermal injection. This reaction was characterized by an exacerbation of clinical symptoms. In vitro, activation of whole blood with Candida albicans antigen was detected by using flow cytometry after staining for activating markers. CD 25 positive T cells were detected in a 7 days culture in all patients. Percentage of CD 25 positive T cells was correlated to the intensity of the local cutaneous DTH reaction. CD 69 positive T cells were detected after a one day culture only in patient who presented a syndromic reaction to intradermal injection.
Subject(s)
Candida albicans/immunology , Hypersensitivity, Delayed/diagnosis , Lymphocyte Activation , Adolescent , Adult , Aged , Antigens, CD/analysis , Antigens, Differentiation, T-Lymphocyte/analysis , Antigens, Fungal/immunology , CD4-Positive T-Lymphocytes/immunology , Female , Flow Cytometry , Humans , Hypersensitivity, Delayed/immunology , Immunoglobulin E/immunology , Intradermal Tests , Lectins, C-Type , Male , Middle Aged , Receptors, Interleukin-2/analysis , T-Lymphocyte Subsets/immunologySubject(s)
Candida albicans/immunology , Hypersensitivity, Delayed , T-Lymphocytes/immunology , Antigens, CD/analysis , Antigens, Differentiation, T-Lymphocyte/analysis , Antigens, Fungal/immunology , CD3 Complex/analysis , Female , Humans , Lectins, C-Type , Lymphocyte Activation , Male , Skin TestsABSTRACT
Although time-consuming and requiring live parasites, the Sabin and Feldman dye test (DT) is still considered the 'gold standard' among the serological tests for toxoplasmosis diagnosis. The present study was initiated to compare detection of dead parasites using optical microscopy with flow cytometry and a fluorescent nonvital dye, propidium iodide. After incubation with sera (N = 150) and a complement source, tachyzoites were washed, then stained using a fluorescein-conjugated Toxoplasma-specific antiserum. Dead tachyzoites were detected by flow cytometry after addition of propidium iodide. Intra- and inter-assay reproducibilities of percentages of dead parasites varied between 7 and 14%, and 8 and 21%, respectively. When comparing flow cytometry with the classical DT, no discrepancy was noted for positive (N = 118) and negative sera (N = 32). Correlation was good (r = 0.85) for positive sera. In conclusion, when easily available, flow cytometry is a very sensitive, specific and time-sparing method to detect specific antibodies to Toxoplasma gondii.