Marker Of Acute Infection Research Articles

C-Reactive Protein Levels Correlate with Measures of Dysglycemia and Gut Microbiome Profiles.

C-reactive protein (CRP) is a commonly used marker of low-grade inflammation as well as a marker of acute infection. CRP levels are elevated in those with diabetes and increased CRP concentrations are a risk factor for developing type 2 diabetes. Gut microbiome effects on metabolism and immune responses can impact chronic inflammation, including affecting CRP levels, that in turn can lead to the development and maintenance of dysglycemia. Using a high-sensitivity C-reactive protein (hsCRP) assay capable of detecting subtle changes in C-reactive protein, we show that higher hsCRP levels specifically correlate with worsening glycemia, reduced microbial richness and evenness, and with a reduction in the Firmicutes/Bacteroidota ratio. These data demonstrate a pivotal role for CRP not only in the context of worsening glycemia and changes to the gut microbiota, but also highlight CRP as a potential target for mitigating type 2 diabetes progression or as a therapeutic target that could be manipulated through the microbiome. Understanding these processes will provide insights into the etiology of type 2 diabetes in addition to opening doors leading to possible novel diagnostic strategies and therapeutics.

Correlation between CRP Level and Stroke Volume

Background: Stroke is an important health issue for individuals and society. Early identification of risk factors of stroke patients helps take measures to prevent the development of further stroke. C-reactive protein is a marker of acute infection as well as acute inflammation. A high level of CRP may be associated with poor outcomes because they reflect either an inflammatory reaction or tissue damage (den Hertog HM et al., 2009). Increase in inflammatory parameters correlated significantly with lesion volume and stroke severity (Audebert HJ et al., 2004). Aim of the study: To see the Correlation between CRP level and stroke volume. And to see the CRP level as a prognostic marker in 3 months follow-ups in ischemic stroke. Methods: This was a descriptive cross-sectional study undertaken in the neurology department of a medical college hospital in Bangladesh. A total of 130 patients were included in the study group who met the inclusion and exclusion criteria. Out of 130 patients, 63 were ischemic strokes and 67 were hemorrhagic strokes. Results: In our study, the estimated level of mean CRP level in acute haemorrhagic stroke was 8.6 mg/L. and in acute ischemic stroke was 21.6mg/L. In this study, there was a statistically significant relationship between the size of the infarct and the level of estimated CRP in ischemic stroke. There was no correlation between CRP level and volume of hemorrhage in hemorrhagic stroke. In this study, the mean CRP value was 19.1 mg/L in those patients who were alive and 28.4 mg/L in those patients who died of ischemic stroke. The difference between the two groups was not statistically significant (p-value 0.30) though the mean CRP in patients who died were much higher than in those who were alive. Conclusion: In conclusion, we believe that these data support two main conclusions. First, the elevation of CRP is common in ischemic stroke. Second, advanced CRP levels were associated with larger infarct size in cases with acute ischemic stroke. These results suggest that elevated CRP levels, reflecting a large infarct size, may serve as a helpful serologic marker in the evaluation of inflexibility of acute ischemic stroke.

Differences in serological profiles of Epstein-Barr virus infection in patients with head and neck tumors and lymphomas.

e18055 Background: Epstein-Barr virus (EBV) is associated with the development of various cancers, including nasopharyngeal carcinoma (NPC), gastric cancer, and lymphomas. The use of EBV serological markers in screening and monitoring of NPC has been shown to be valuable. The significance of serological markers in the diagnosis of other head and neck cancers is poorly described. The aim of this study was to analyze the serological profiles of EBV infection in patients with head and neck tumors. Methods: The main group included 24 patients with laryngeal cancer (n = 12) and oral mucosa cancer (n = 12). Keratinizing squamous cell carcinoma was registered in 22 (91.7%) patients, and adenoid cystic cancer in 2 (8.3%) patients. The control group included 44 lymphoma patients. Antibodies to EBV proteins were determined in the blood serum by ELISA and Western blot (WB) tests. Results: ELISA detected antibodies of the A, M and/or G classes against various EBV proteins in 100% of patients in the main group and 97.7% of controls. IgA VCA in patients with head and neck cancer were determined 2.7 times more often (50% vs 18.2%, p = 0.034) than in patients with lymphomas, IgG EA - 2.1 times more often (58.3% vs 27.3%, p = 0.049), and the complex of acute infection markers (IgA VCA, IgM VCA, IgG EA in various combinations) was determined 2.0 times more often (66.7% vs 34.1%, p = 0.045). Atypical profile (only VCA IgG+) was determined only in patients with lymphomas (4.5%). The profile characteristic of immunosuppression (IgG VCA+, IgG EA+, NA IgG±) was determined 1.8 times more often in patients with head and neck cancer than in patients with lymphomas (25% vs 13.6%, p > 0.05). According to WB tests, patients of the main group more often demonstrated IgM EBNA-1p79 (16.7%), VCA p65 (16.7) and p22 (16.7%), while controls – VCA p22 (27.8%), EA-R p93 (16.7%) and VCA p33 (16.7%). IgG in the main group was more often determined to EBNA-1 p79 (91.7%), VCA p22 (91.7%) and VCA p33 (66.7%), in the control group to VCA p40 (87.5%), EBNA-1 p79 (75%) and VCA p22 (62.5%). Statistically significant differences were found only for VCA p42 (0% in the experimental group and 37.5% in controls, p = 0.049), VCA p40 (25% and 87.5%, p = 0.009) and p27 (0% and 37.5%, p = 0.049). EA-D p45 was determined only in patients with lymphoma. Conclusions: The vast majority of patients in both groups were previously infected with EBV. Serological profiles of EBV infection in patients with head and neck cancer and lymphomas were significantly different. Markers of acute infection were more often determined in patients with head and neck cancer; the range of individual proteins in the main group was narrower than in the control group. The biological meaning of the differences in the detection rates of antibodies to individual EBV proteins in patients of the two groups remains to be elucidated.

Febrile palpebral edema

Febrile palpebral edema

The frequency of detection of markers of Сytomegalovirus infection in children with recurrent respiratory diseases in patients with Shiga-toxin-associated hemolytic-uremic syndrome (STEC-HUS)

The paper presents data on the detection and role of cytomegalovirus infection (CMVI) in 146 children of certain groups aged from 3 months to 15 years who were hospitalized — frequently ill children with respiratory pathology, patients with shiga-toxin-associated hemolytic uremic syndrome (STEC-HUS) and schoolchildren with somatic diseases during rehabilitation in a sanatorium.The aim of the study was to determine the frequency of detection of CMVI in the presented groups, the originality of the main clinical manifestations in correlation with the markers of activity of herpesvirus type V infection. Clinical monitoring was carried out, oropharyngeal swabs, saliva,blood samples (serum and blood cells) were studied using a set of laboratory diagnostic methods:RCM (rapid culture method) on Vero- and M-19 cells, IIR (reaction of indirect immunofluorescence), ELISA to detect specific antigens and antibodies (IgM, IgG).The detection rate of CMV IgG in diagnostic values ranged from 6.4% in the group of frequently ill children with respiratory pathology to 31.7% in schoolchildren of the sanatorium, the acute course of infection was detected in3.2% and 6.4%, respectively, based on markers of acute infection (CMV IgM and cytomegalovirus antigen). In patients with STEC-HUS CMV IgG in diagnostic titers were recorded with the highest frequency — in 74.4% of patients.

Neutrophil extracellular traps: diagnostic and prognostic value in COVID-19

Rationale: An important element of antiviral defense in the pathophysiology of COVID-19 is the innate cell immunity including polymorphonuclear neutrophils prone to netotic transformation. Neutrophils can be not only a marker of acute infection, but, being a source of neutrophil extracellular traps (NET), can play a key role in the development of thrombotic complications leading to acute respiratory insufficiency in COVID-19.Aim: To determine the diagnostic and prognostic value of NET levels in patients with COVID-19.Materials and methods: We monitored NET levels in peripheral blood of 34 patients with COVID-19 (mean age, 67 ± 15.8 years), admitted to MONIKI hospital. The control group consisted of 54 healthy volunteers (mean age, 52 ± 11.5 years). Whole blood samples of 2 pL each were used for the preparation of monolayer smears (Giemsa stain) and calculation of at least 200 cell structures including native intact and transformed neutrophils (MECOS-C2 microscope, Medical computer systems).Results: Patients with COVID-19 had higher NET levels, compared to those in healthy controls: 14.5% (2.9-28.6%) vs. 5.0% (1.8-11.9%, p < 0.0001). The patients who were on non-invasive respiratory support (23.5%) had a NET level of 12% (8.122.3%), whereas those on invasive mechanical ventilation (17.6%) had a 1.5-fold higher NET level of 17.9% (12.3-28.2%) (p < 0.05). In the patients who died (11.8% of the cases), the NET level amounted to 19% (16.5-26%, p < 0.05). Monitoring of blood NET levels was performed in 9 patients from the day of admittance to the day of their transfer to the intensive care unit / discharge / death. It was shown that a decrease of NET levels mirrors an improvement of the patient's clinical condition and efficacy of his/hers treatment. On the opposite, an increase of NET levels can indicate a deterioration and risk of unfavorable course.Conclusion: We have identified some pathophysiological mechanisms in COVID-19, related to the neutrophil compartment. Patients with coronavirus infection are characterized by high NET levels which is at least 3-fold higher than that in healthy volunteers. This indicates an abnormality in immune host defense and development of an inadequate inflammatory response. An increase of NET in whole blood smears of more than 16% can be a criterion of an unfavorable prognosis of the disease course and the risk of death.

Potential value of serum Aspergillus IgG antibody detection in the diagnosis of invasive and chronic pulmonary aspergillosis in non-agranulocytic patients

BackgroundAt present, serum Aspergillus IgG and IgM antibody detection is mainly used in the diagnosis of chronic pulmonary aspergillosis (CPA), but its value in the diagnosis of invasive pulmonary aspergillosis (IPA) in non-agranulocytic patients is still unclear. IgM can be used as a marker of acute infection to help diagnose acute infection-related diseases. IgG is a marker of long-term infection and is used to assist in the diagnosis of pre-existing or chronic infection-related diseases. The aim of this study was to investigate and compare the value of serum Aspergillus IgG and IgM antibody detection in the diagnosis of IPA and CPA in non-agranulocytic patients.MethodsFifty-eight cases of pulmonary aspergillosis (37 IPA and 21 CPA cases), 15 cases of community-acquired bacterial pneumonia and 50 cases in the healthy control group were collected. The serum (1,3)-β-D-glucan test (G test) was performed with a chromogenic method, and the galactomannan test (GM test) and Aspergillus IgG and IgM antibody detection were performed by commercial enzyme-linked immunosorbent assay (ELISA) in all patients. The sensitivity and specificity, cut-off value and area under the curve (AUC) of Aspergillus IgG and IgM antibodies were further obtained by receiver operating characteristic (ROC) curves.ResultsThe positive rate of the G test, Aspergillus IgG antibody detection and the GM test also showed notable differences among the IPA, CPA, community-acquired bacterial pneumonia and healthy groups (P = 0.006, P < 0.001 and P = 0.217, respectively). Only the positive rate of the GM test showed a significant difference between the IPA and CPA groups (P = 0.04). ROC curves indicated that Aspergillus IgG antibody detection had a higher specificity in the IPA group than in the CPA group (0.952). The detection of Aspergillus IgG antibody can preferably distinguish IPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.923, specificity = 0.459, cut-off value = 134.46, AUC = 0.727). It can also distinguish CPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.952, specificity = 0.692, cut-off value = 75.46, AUC = 0.873).ConclusionsSerum Aspergillus IgG antibody detection may have certain clinical value in the diagnosis of IPA and CPA in non-agranulocytic patients.

Common Host Responses in Murine Aerosol Models of Infection Caused by Highly Virulent Gram-Negative Bacteria from the Genera Burkholderia, Francisella and Yersinia.

Highly virulent bacterial pathogens cause acute infections which are exceptionally difficult to treat with conventional antibiotic therapies alone. Understanding the chain of events that are triggered during an infection of a host has the potential to lead to new therapeutic strategies. For the first time, the transcriptomic responses within the lungs of Balb/C mice have been compared during an acute infection with the intracellular pathogens Burkholderia pseudomallei, Francisella tularensis and Yersinia pestis. Temporal changes were determined using RNAseq and a bioinformatics pipeline; expression of protein was also studied from the same sample. Collectively it was found that early transcriptomic responses within the infected host were associated with the (a) slowing down of critical cellular functions, (b) production of circulatory system components, (c) lung tissue integrity, and (d) intracellular regulatory processes. One common molecule was identified, Errfi1 (ErbB receptor feedback inhibitor 1); upregulated in response to all three pathogens and a potential novel marker of acute infection. Based upon the pro-inflammatory responses observed, we sought to synchronise each infection and report that 24 h p.i. of B. pseudomallei infection closely aligned with 48 h p.i. of infection with F. tularensis and Y. pestis. Post-transcriptional modulation of RANTES expression occurred across all pathogens, suggesting that these infections directly or indirectly modulate cell trafficking through chemokine expression/detection. Collectively, this unbiased NGS approach has provided an in-depth characterisation of the host transcriptome following infection with these highly virulent pathogens ultimately aiding in the development of host-directed therapies as adjuncts or alternatives to antibiotic treatment.

No Correlation Between Nasopharyngeal Human Bocavirus 1 Genome Load and mRNA Detection or Serology in Adeno-/Tonsillectomy Patients.

Human bocavirus 1 (HBoV1) can persist in nasopharynx and tonsils. Using HBoV1 serology, reverse-transcription polymerase chain reaction (PCR) for detecting messenger RNA (mRNA) and quantitative PCR for HBoV1 genome load count, we studied to what extent the HBoV1 DNA loads in nasopharynx correlate with acute infection markers. Tonsillar tissue, nasopharyngeal aspirate, and serum were obtained from 188 elective adeno-/tonsillectomy patients. Relatively high loads of HBoV1 DNA were detected in the nasopharynx of 14 (7%) primarily asymptomatic subjects with negative mRNA and/or serodiagnostic results. Quantitative HBoV1 DNA PCR may have lower specificity than HBoV1 mRNA detection for diagnosing symptomatic infection.

Evaluation of Protective Immune Response Induced by a DNA Vaccine Encoding GRA8 against Acute Toxoplasmosis in a Murine Model.

Toxoplasma gondii is an apicomplexan zoonotic protozoan parasite that infects most species of warm-blooded animals, including humans. The heavy incidence and severe or lethal damage caused by T. gondii infection clearly indicate a need for the development of an effective vaccine. T. gondii GRA8 is a member of the dense granules protein family and is used as a marker of acute infection. In the present study, we evaluated the protective immunity induced by DNA vaccination based on a recombinant eukaryotic plasmid, pDsRed2-GRA8, against acute toxoplasmosis in mice. BALB/c mice were intramuscularly immunized with the pDsRed2-GRA8 plasmid and then challenged by infection with the highly virulent GFP-RH strain of T. gondii. The specific immune responses and protective efficacy against T. gondii of this vaccine were analyzed by measuring cytokine and serum antibody titers, splenocyte proliferation assays, and the survival times of mice after challenge. Our results showed that mice immunized with pDsRed2-GRA8 demonstrated specific humoral and cellular responses, induced higher IgG antibody titers with predominant IgG2a production; increased levels of IL-10, IL-12 (p70), IFN-γ, TNF-α, and splenocyte proliferation; and prolonged survival times compared to those of control mice. The present study showed that DNA immunization with pDsRed2-GRA8 induced humoral and cellular immune responses, and all immunized mice showed greater Th1-type immune responses and longer survival times than those of control mice. These results indicated that T. gondii GRA8 DNA immunization induces a partial protective effect against acute toxoplasmosis.

Antibiotic use as a marker of acute infection and risk of first and recurrent venous thrombosis.

A role for transient infections in the aetiology of venous thrombosis (VT) has been suggested. This study aimed to determine whether individuals who receive antibiotic treatment (as a proxy for infections) have an increased risk of first and recurrent VT and whether infections should be seen as a provoking risk factor for VT. We used the self-controlled case series method to study the risk of first VT during antibiotic prescriptions. The risk of recurrent VT during antibiotic use was estimated by of time-dependent Cox-regression. A total of 2547 patients with a first VT were included and followed for a median of 5·9years for recurrence (1999-2010), in whom 114 first events occurred during antibiotic use. We found a five-fold increased risk of first VT during antibiotic treatment: [incidence-rate-ratio 5·0; 95% confidence interval (CI), 4·0-6·1]. Antibiotic use was associated with a 2·0-fold (95% CI, 1·1-4·0) increased risk of recurrent VT. Patients with an unprovoked first VT who used antibiotics shortly before this event, had a similar risk of recurrence as patients with a provoked first VT (adjusted hazard ratio 1·1; 95% CI, 0·7-1·7). Individuals who receive antibiotics have an increased risk of first and recurrent VT and infections should be considered a provoking risk factor for VT.

Association of Severity of Coronary Lesion with Markers of Acute Infection and Inflammation in Patients with Acute Coronary Syndrome

Association of Severity of Coronary Lesion with Markers of Acute Infection and Inflammation in Patients with Acute Coronary Syndrome

Von Mäusen auf Menschen – Erkenntnisse aus der Hantavirus-Epidemie 2010

With 2017 notified cases the largest hantavirus epidemic in Germany has occurred in 2010. We report on two interesting cases illustrating the wide range of the individual clinical course and the diagnostic problems in hantavirus disease. The first patient was a seriously ill 44-year-old man who needed dialysis after an onset of flu-like symptoms with oliguria. An initially negative result of a hantavirus serology focused attention on rapidly progressive glomerulonephritis. The second patient, a 22-year-old man, presented with severe neurological symptoms with seizures. Pathological examination of the renal-biopsy specimen in Case 1 reportedly showed the typical pattern of tubulointerstitial damage in the renal cortex and the outer medulla as in hantavirus infection. In a repeated analysis Puumala virus RNA as a marker of acute infection was found. After dialysis and administration of higher-dose systemic glucocorticoids the patient slowly recovered. In Case 2 the severe neurological symptoms caused a complete neurological diagnostic with lumbar puncture and MRI before the detection of specific antibodies and Puumala virus RNA showed that nephropathia epidemica was the disease. The patient recovered after 10 days. Because of the variability of symptoms and the extrarenal manifestations of the disease the nephropathia epidemica can occasionally cause problems of differential diagnosis. A rapid diagnosis is important because of the urgent differentiation of other renal diseases with bad prognosis.

Comparison of neutrophil volume distribution width to C-reactive protein and procalcitonin as a proposed new marker of acute infection

The aim of this study was to assess the use of neutrophil distribution width (NDW) and to compare it to C-reactive protein (CRP) and procalcitonin (PCT), in the detection of early sepsis in the intensive care unit. Subjects (N = 166) were divided into 4 groups: healthy, acute inflammatory non-infectious (AINI), localized infection, and systemic infection, according to clinical history and cultures. NDW, CRP, and PCT were compared among the different groups using multivariate analysis of variance (MANOVA). Diagnostic efficacy was assessed using receiver operating characteristic curves and areas under the curves (AUC). The lowest mean(NDW) was found in the healthy group (n = 41), followed by the AINI (n = 20), localized infection (n = 55), and systemic infection (n = 50) groups. AUC(NDW) was 0.877 for infected (localized + systemic) vs non-infected (healthy + AINI) groups, and 0.965 for systemic infection vs non-infected groups. A cut-off of 21.9 resulted in 90% sensitivity, 92% specificity, 90% positive predictive value, and 92% negative predictive value (AUC(NDW) = 0.965, 95% confidence interval 0.935-0.995). According to MANOVA, only NDW was able to differentiate an acute inflammatory process from early infection in postoperative patients, but not healthy from AINI subjects. NDW had the highest diagnostic accuracy and is available with the complete blood count with differential (CBC). It may be a promising parameter to aid in the diagnosis of acute infection in adults, provided the possibility of haematological disorders is first ruled out.

Analysis of the acute phase responses of Serum Amyloid A, Haptoglobin and Type 1 Interferon in cattle experimentally infected with foot-and-mouth disease virus serotype O

A series of challenge experiments were performed in order to investigate the acute phase responses to foot-and-mouth disease virus (FMDV) infection in cattle and possible implications for the development of persistently infected "carriers". The host response to infection was investigated through measurements of the concentrations of the acute phase proteins (APPs) serum amyloid A (SAA) and haptoglobin (HP), as well as the bioactivity of type 1 interferon (IFN) in serum of infected animals. Results were based on measurements from a total of 36 infected animals of which 24 were kept for observational periods exceeding 28 days in order to determine the carrier-status of individual animals. The systemic host response to FMDV in infected animals was evaluated in comparison to similar measurements in sera from 6 mock-inoculated control animals.There was a significant increase in serum concentrations of both APPs and type 1 IFN in infected animals coinciding with the onset of viremia and clinical disease. The measured parameters declined to baseline levels within 21 days after inoculation, indicating that there was no systemically measurable inflammatory reaction related to the carrier state of FMD. There was a statistically significant difference in the HP response between carriers and non-carriers with a lower response in the animals that subsequently developed into FMDV carriers. It was concluded that the induction of SAA, HP and type 1 IFN in serum can be used as markers of acute infection by FMDV in cattle.

Identification of Toxoplasma gondii SUB1 Antigen as a Marker for Acute Infection by Use of an Innovative Evaluation Method

By the separation of Toxoplasma lysate using two-dimensional gel electrophoresis and its analysis with human serum samples and mass spectrometry, the subtilisin-like protein (SUB1) was identified to be a potential marker for acute toxoplasmosis. Following expression of the C-terminal domain of SUB1 in Escherichia coli, it was tested in a line blot assay using a total of 80 human serum samples. Two computer programs based on different evaluation strategies were used for judgment of the line blot results: (i) a time-dependent method with a predefined cutoff value and (ii) a fixed-time-point method with a calculated cutoff. Thereby, SUB1 was proven to be rather reactive with specific immunoglobulin A (IgA), IgM, and IgG of patients with an acute infection. This finding makes this antigen an attractive candidate for improving diagnosis of toxoplasmosis and demonstrates that not only the selection of respective antigens but also the evaluation method chosen are important for the evaluation of new diagnostic markers.

Eosinopenia as a marker of mortality and length of stay in patients admitted with exacerbations of chronic obstructive pulmonary disease

Blood eosinopenia has long been known as a marker of acute infection, and has recently been shown to be a better predictor of sepsis than CRP in critically ill patients. This study examines the usefulness of eosinopenia (< or = 0.04), for predicting the severity of exacerbations of COPD using inpatient mortality and length of stay as markers of severity. Retrospective review of the case-notes of patients admitted with an exacerbation of COPD from March 2007 to April 2008. Patients with radiographic evidence of pneumonia and those having steroids in the previous week were excluded. Data were collected for age, length of stay, pH, WCC and mortality. Sixty-five patients fulfilled the inclusion criteria, 42 with a normal eosinophil count and 23 with eosinopenia. No significant differences were seen between the two groups' age, total WCC and admission pH. However, significant differences were seen in mortality (4/23 (17.4%) vs 1/42 (2.4%), P = 0.049) and length of stay (8 vs 5 days, P = 0.005) when the eosinopenia group compared with those with normal eosinophils. The eosinophil count might be a useful marker of severity inpatients admitted with an exacerbation of COPD independent of the WCC and pH. As it is routinely given in the full blood count in all patients admitted to hospital, there is no extra cost for this beneficial test.

Clinical utility of avidity assays

IgM may persist for months, presenting a risk of an erroneous diagnosis where serology is the only available tool. Indeed, IgM may be detected in secondary infection as a result of crossreactivity and/or nonspecific stimulation of the immune system. One test that can aid the serologist is IgG avidity testing, in that the avidity of IgG is low early in infection with the avidity of IgG antibodies increasing over time. Congenital toxoplasmosis can induce serious sequelae. Detectable IgM usually persists long after the acute infection. IgG avidity can be an important aid in diagnosis and assessing the risk to the fetus. Another infection that is of concern in pregnancy is cytomegalovirus (CMV). In pregnant women it is very important to differentiate primary from secondary infection, as primary infection presents the highest risk to the fetus. Serologic detection of IgM alone is not a specific marker of primary CMV infection. IgG avidity can have utility in identifying or excluding primary CMV infections during pregnancy. Outside of pregnancy, IgG avidity testing is increasingly recognized as a valuable tool. During the recent West Nile virus (WNV) epidemic in the US, it was recognized that WNV-specific IgM may persist for 6 - 12 months following exposure. Thus, a person presenting to their clinician with nonspecific symptoms may be tested and return a positive WNV IgM that may be the product of exposure during the previous period. In this environment, WNV IgG avidity testing is able to provide some assistance. IgG avidity testing should not be used alone and without an understanding of the limitations of the technique. Serology remains an important tool for the diagnosis and management of infectious disease. Classically, IgM is defined as a marker of acute infection and IgG, in the absence of clinical disease, is often considered a marker of past infection. However, the clinical reality can be quite different.

IgG avidity assay firms up the diagnosis of acute toxoplasmosis on the first serum sample in immunocompetent pregnant women

Rapid diagnosis of acute toxoplasmosis during pregnancy permits timely treatment and prevents or attenuates congenital toxoplasmosis. Specific IgM antibodies to Toxoplasma as marker of acute infection are often poorly informative, meaning that a complementary technique is needed to reach a diagnosis on the first sample. Here we evaluated 2 commercial kits designed to assist with the diagnosis of acute toxoplasmosis: Platelia® Toxo IgG Avidity Complementary Reagents and Platelia® Toxo IgA, both from BIO-RAD (Marnes La Coquette, France). We tested 2 groups of subjects: 36 patients with acute toxoplasmosis and 55 patients with chronic toxoplasmosis. The IgG avidity test had a sensitivity of 100% (36/36), a specificity of 92.7% (51/55), a positive predictive value of 90%, and a negative predictive value of 100%. Among the immunocompetent women population, the avidity test had perfect sensitivity and specificity, and positive and negative predictive values of 100%. The IgA test had a sensitivity of 88.8% (32/36) and a specificity of 85.4% (47/55), and positive and negative predictive values of 80% and 92.1%, respectively. When the 2 tests were combined, there was only 1 case in which the diagnosis of chronic toxoplasmosis could not be confirmed. The IgG avidity test can therefore be used to rapidly distinguish between chronic and acute infection on the first sample from a pregnant woman, provided there is no underlying immunodepression and no ongoing antitoxoplasmic treatment. In these 2 situations, the results must be interpreted with care, and other serologic markers, including IgA, should be tested. Determination of a pregnant woman's status on a first serum sample allows therapeutic and preventive management to be started without delay.

Viral Infection Induced Acute Megaloblastic Anemia: A Case Series.

We have documented a series of ten patients presenting with symptomatic anemia and a recent history of constitutional symptoms such as fever, myalgias and diarrhea. They were mildly icteric and had severe pallor. Lymphadenopathy and organomegaly were absent. Peripheral blood smears showed reactive lymphocytes, which are typically seen in viral infections and in addition severe megaloblastic changes consisting of hypersegmentation of neutrophils, macro ovalocytes, leukopenia and thrombocytopenia were noted. Indirect bilirubinemia, elevated serum LDH and low haptoglobins were documented. Direct Coombs was negative in all the patients. Bone marrow aspiration revealed megaloblastic changes. Autoimmune hemolytic anemia, Pernicious anemia, Malaria, T.T.P, Aplastic anemia and HIV were excluded in all the patients. They had diagnostically low serum cobalamin and folate levels and the cytopenias normalized with parenteral vitamin supplementation. None of the patients received steroids or antiviral treatment.Was the viral syndrome causally related to the megaloblastic anemia or was a preexisting megaloblastic anemia being brought to the attention of the clinician by the acute viral syndrome? This puzzling question was solved when a patient who had a normal complete blood count in March 2005 at our institute, developed severe pancytopenia after a febrile illness in October 2005. Another patient in the series had normal hemoglobin and had actually donated a unit of blood one month prior to his admission with diarrhea and severe pancytopenia.The next question that we faced was regarding the identity of the virus. We initially performed a lymphadenitis panel (Euro Immune) consisting of 16 common viral markers. Epstein Barr virus (EBV) was positive in the initial case. An EBV Immunofluorescence panel (Euro Immune) was done in all the subsequent patients. This test was positive in 6 out of the10 patients, they were positive for EBV Capsid IgG, EBV Capsid IgM, and EBV early antigen Ig G (acute infection markers). EBV nuclear antigen IG G (chronic infection marker) was negative.It should be noted that none of the patients had neurological deficits despite having diagnostically low cobalamine levels and this we presume is due to the acute onset of illness not allowing enough time for the development of neurological symptoms. There were quite a few patients seen in this period of time with typical EBV infection without any megaloblastic changes and similarly there were patients with overt megaloblastic anemia without any features of EBV infection. Hence there must be a patient specific characteristic that predisposes them to acute megaloblastic anemia on developing the viral infection. Since only two of these ten patients are pure vegans and since none were malnourished we have to look for a non nutritional cause for this predisposition. An acute coombs negative hemolytic anemia due to the viral infection can explain the cytpenias but the low B12 levels and the prompt response to B12 supplementation are unexplained.We feel that this is a new syndrome of reversible viral induced acute onset megaloblastic anemia. There exists a possibility that this is a new strain of EBV virus, and we have stored the sera of all the patients for future epidemiological purposes. We are recommending that physicians should consider B12/folate supplementation in acute EBV syndromes and obtain follow-up CBC one month after the illness. We believe that further work has to be done before a definite association between EBV and megaloblastic anemia can be established.