Evaluation of Immunodiagnostic Tests for Leprosy in Brazil, China and Ethiopia.

Leprosy remains persistently endemic in several low- or middle income countries. Transmission is still ongoing as indicated by the unabated rate of leprosy new case detection, illustrating the insufficiency of current prevention methods. Therefore, low-complexity tools suitable for large scale screening efforts to specifically detect M. leprae infection and diagnose disease are required. Previously, we showed that combined detection of cellular and humoral markers, using field-friendly lateral flow assays (LFAs), increased diagnostic potential for detecting leprosy in Bangladesh compared to antibody serology alone. In the current study we assessed the diagnostic performance of similar LFAs in three other geographical settings in Asia, Africa and South-America with different leprosy endemicity. Levels of anti-PGL-I IgM antibody (humoral immunity), IP-10, CCL4 and CRP (cellular immunity) were measured in blood collected from leprosy patients, household contacts and healthy controls from each area. Combined detection of these biomarkers significantly improved the diagnostic potential, particularly for paucibacillary leprosy in all three regions, in line with data obtained in Bangladesh. These data hold promise for the use of low-complexity, multibiomarker LFAs as universal tools for more accurate detection of M. leprae infection and different phenotypes of clinical leprosy.

Profile of Rheumatological Manifestations in Leprosy in a Tertiary Care Hospital from Himachal Pradesh.

The rheumatological manifestations of leprosy occur singly or in varying combinations, particularly during lepra reactions. Despite being third most common, these remain under diagnosed and under reported. This study has been carried out to study the spectrum of rheumatological manifestations in leprosy patients. One hundred consecutive patients of leprosy presenting during January to December 2013 were studied for rheumatological manifestations. Complete hemogram, serum biochemistry, urinalysis, rheumatoid factor, ASO titer, C-reactive protein, ANA, and x-rays for hands, feet, chest and involved joints were performed. These 100 (M:F 66:34) patients aged between 16-80 years had indeterminate (2 patients), TT (4 patients), BT (26 patients), BB (2 patients), and LL leprosy (32 patients). 27 patients had rheumatological manifestations; arthritis involving large or small joints in 23 patients being the commonest. 7 of 24 patients in type-1 lepra reaction had enthesitis in 3 patients and oligoarthritis in 4 patients. Rheumatoid arthritis-like polyarthritis was noted in 19 patients with type-2 reaction. Tenosynovitis, dactylitis, bony changes were also noted. Except for one case, these features were present in patients having lepra reactions. Rheumatoid factor in 14, ANA in 15, C-reactive protein in 45 cases was positive. ASO was positive 34 cases. Symmetrical polyarthritis involving small joints of hands and feet, oligoarthritis, enthesitis and dactylitis are common in leprosy particularly with borderline leprosy, type-2 lepra reaction especially in the presence of positive RAfactor.

Prevalence and clinical patterns of psoriatic arthritis in Indian patients with psoriasis.

BACKGROUND: The prevalence and clinical patterns of psoriatic arthritis (PsA) varies in different parts of the world and there is little clinical and epidemiological data from the Indian subcontinent. AIMS: Our study was designed to evaluate the prevalence and clinical patterns of PsA in Indian patients. METHODS: This was a non-interventional, cross-sectional study, in which 1149 consecutive psoriasis patients seen over 1 year were screened for PsA according to classification of psoriatic arthritis (CASPAR) criteria. Demographic and disease parameters were recorded including Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), and number of swollen and tender joints. RESULTS: Among 1149 patients with psoriasis, 100 (8.7%) patients had PsA, of which 83% were newly diagnosed. The most common pattern was symmetrical polyarthritis (58%), followed by spondyloarthropathy 49%, asymmetric oligoarthritis (21%), isolated spondyloarthropathy (5%), predominant distal interphalangeal arthritis (3%), and arthritis mutilans (1%). Enthesitis and dactylitis were present in 67% and 26% of cases, respectively. The mean number of swollen and tender joints were 3.63±3.59 (range, 0-22) and 7.76±6.03 (range, 1-26), respectively. Nail changes were present in 87% of the cases. The median PASI and NAPSI of the subjects with PsA was 3.6 and 20, respectively. There was no significant correlation of number of swollen/tender joints with PASI or NAPSI. CONCLUSION: There is a relatively low prevalence of PsA among Indian psoriasis patients presenting to dermatologists. No correlation was found between the severity of skin and nail involvement and articular disease.

Difference of dilation resistance to coronary stenting between fibrous plaques and lipid-rich plaques.

BACKGROUND: Dilation resistance to stenting in non-calcified coronary plaques was compared in patients with percutaneous coronary intervention (PCI) in order to confirm the clinical usefulness of multislice computed tomography in examining coronary plaque type and to provide information pertaining to the effects of plaque type on dilatation resistance. METHODS: A retrospective analysis of 64-slice computed tomography coronary imaging data collected in the month prior to coronary stenting in 93 patients (65 male and 28 female, mean age of (57.22±7.22) years) was conducted. Non-calcified coronary plaques were divided into lipid-rich (lipid content >25% of plaque volume) and fibrous plaques according to the Hammer-Hansen S method: where lipids, fiber, and intraluminal components were indicated by contrast using Hu values of -100-49, 50-129, and >130, respectively. Clinical features, pre-dilatation balloon specifications and filling pressure, and stent size and release pressure were compared. RESULTS: High-sensitivity C-reactive protein levels were higher in the lipid-rich plaque group. In patients with typical symptoms, unstable angina was more commonly observed in the lipid-rich plaque group. No significant differences in low density lipoprotein, pre-dilatation balloon specifications, pre-dilatation pressure, or stent specifications were observed. Stent release pressure in the lipid-rich plaque group ((1130.16±202.04) kPa), was significantly lower than that observed in the fibrous plaque group ((1240.61±193.29) kPa, P = 0.009). CONCLUSION: Softer, lipid-rich plaques exhibit lower dilation resistance during stenting in PCI patients.

No relationship between lung function and high-sensitive C-reactive protein in adolescence.

INTRODUCTION: Several studies on adults have indicated that lower spirometric lung function may be associated with increased systemic inflammation, but no studies have investigated if this association is already present in adolescence. OBJECTIVE: We explored the temporal relationship between changes in lung function and concentrations of plasma C-reactive protein (CRP) in a population-based cohort study at ages 14 and 20 years using a high-sensitivity CRP assay. METHODS: CRP measurements were performed in a total of 420 subjects at mean age of 13.9 years. Of these, 262 subjects (62%) participated in the follow-up investigation at mean age of 20.1 years. RESULTS: Levels of log-CRP at age 14 were not significantly associated with forced expiratory volume (FEV(1) ) or FEV(1) / forced vital capacity (FVC) ratio at age 20, nor with the change in FEV(1) , FVC or FEV(1) /FVC ratio between 14 and 20 years after controlling for body mass index (BMI), airway hyperresponsiveness (AHR), eosinophil cationic protein (ECP), asthma, smoking, sex, and height at 14 years, and change in height between 14 and 20 years. Sex, BMI, AHR, ECP and change in height between 14 and 20 years were identified as independent factors associated with the change in FEV(1) , FVC and FEV(1) /FVC ratio in adolescence. CONCLUSION: We did not find an association between CRP levels at age 14 and change in lung function by age 20; whereas, sex, change in height, BMI, AHR and ECP were associated with lung function change in adolescence. Our findings indicate that systemic inflammation is of less importance for change in lung function in adolescence. Please cite this paper as: Nybo M, Hansen HS, Siersted HC and Rasmussen F. No relationship between lung function and high-sensitive C-reactive protein in adolescence.

Thalidomide suppressed IL-1beta while enhancing TNF-alpha and IL-10, when cells in whole blood were stimulated with lipopolysaccharide.

Thalidomide is used to treat erythema nodosum leprosum (ENL). The events that precipitate this inflammatory reaction, which may occur in multibacillary leprosy patients, and the mechanism by which thalidomide arrest ENL, are not known. Thalidomide's ability to inhibit tumor necrosis factor alpha (TNF-alpha) in vitro has been proposed as a partial explanation of its effective treatment of ENL. In in vitro assays, thalidomide can enhance or suppress TNF-alpha. This is dependent on the stimulant used to evoke TNF-alpha; the procedure used to isolate the mononuclear cells from blood, and the predominant mononuclear cell type in the culture. To avoid artifacts that may occur during isolation of mononuclear cells from blood, we stimulated normal human blood with LPS and evaluated the effect of thalidomide and dexamethasone on TNF-alpha, and other inflammatory cytokines and biomarkers. Thalidomide suppressed interleukin 1 beta (IL-1beta) (p = 0.007), and it enhanced TNF-alpha (p = 0.007) and interleukin 10 (IL-10) (p = 0.031). Dexamethasone enhanced IL-10 (p = 0.013) and suppressed IL-1beta, TNF-alpha, interleukin 6 (IL-6), and interleukin 8 (IL-8) (p = 0.013). The two drugs did not suppress: C-reactive protein (CRP), Ig-superfamily cell-adhesion molecule 1 (ICAM 1), tumor necrosis factor receptor 1 (TNFR1), tumor necrosis factor receptor 2 (TNFR2), or amyloid A. In vitro and in vivo evidence is accumulating that TNF-alpha is not the primary cytokine targeted by thalidomide in ENL and other inflammatory conditions.

Utility of measuring serum levels of anti-PGL-I antibody, neopterin and C-reactive protein in monitoring leprosy patients during multi-drug treatment and reactions.

OBJECTIVE: To verify the validity of measuring the levels of Mycobacterium leprae-specific anti-phenolic glycolipid (PGL)-I antibody, neopterin, a product of activated macrophages, and C-reactive protein (CRP), an acute phase protein, in serial serum samples from patients for monitoring the leprosy spectrum and reactions during the course of multi-drug treatment (MDT). METHODS: Twenty-five untreated leprosy patients, 15 multi-bacillary (MB) and 10 paucibacillary (PB), participated. Eight patients developed reversal reaction and five developed erythema nodosum leprosum (ENL) during follow-up. The bacterial index (BI) in slit-skin smears was determined at diagnosis and blood samples collected by venipuncture at diagnosis and after 2, 4, 6 and 12 months of MDT. PGL-I antibody and neopterin were measured by enzyme-linked immunosorbent assay, whereas the CRP levels were measured by the latex agglutination method. RESULTS: The levels of PGL-I antibodies and neopterin were higher in the sera of MB than PB patients, which correlated with the patients' BI. The serum levels of CRP did not differ significantly between the MB and PB patients. The serum levels of PGL-I and neopterin were no higher in reactional patients than non-reactional patients prone to such reactions. However, ENL patients had higher serum CRP levels than non-reactional MB patients. The serum PGL-I antibody levels declined significantly during MDT, in contrast to neopterin and CRP levels. CONCLUSION: Measuring the serum levels of PGL-I antibodies and neopterin appeared to be useful in distinguishing MB from PB patients, whereas monitoring the levels of PGL-I antibodies appeared to be useful in monitoring MB patients on MDT. Measuring serum CRP, although not useful in monitoring the patients, has limited significance in detecting ENL reactional patients.

The routine use of C-reactive protein in forensic investigations.

In clinical medicine, C-reactive protein (CRP) is extensively used as a general marker for immune system activation, and post-mortem applicability has been established [M.Q. Fujita, B.L. Zhu, K. Ishida, L. Quan, S. Oritani, H. Maeda, Serum C-reactive protein levels in postmortem blood-an analysis with special reference to the cause of death and survival time, Forensic Sci. Int. 130 (2002) 160-166; L. Uhlin-Hansen, C-reactive protein (CRP), a comparison of pre- and post-mortem blood levels, Forensic Sci. Int. 124 (2001) 32-35]. We have analysed the routine use of CRP in non-selected cases. Scarcity of blood available for analysis is a common problem in forensic investigation, and in response to this we have developed a method using liver as a source. In 50 consecutive autopsy cases, we have evaluated method, validated results and discussed their interpretation. In three cases the analysis was not possible. For each of the remaining cases (n=47) we have analysed whole blood, serum and/or liver samples. 57% (n=25) had serum CRP > 10 mg/L. Serum levels were higher than in whole blood or liver. CRP levels in serum and whole blood samples were stable in more than one month after death, making storage for later analysis possible. Liver levels peaked at one week, but after one month putrefaction was obvious. CRP levels were independent of the post-mortem interval. The use of liver as a source has not yet been described in literature. Our results in liver samples correlate well with plasma results, and liver is a good post-mortem alternative when blood is not available. We conclude that CRP measurements are easy, viable and inexpensive in a forensic setting, and that the number of cases with CRP elevation is high in a non-selected forensic material. In cases of doubt, marked elevation of CRP is an indicator of natural mode of death, and in cases of trauma, it indicates vital reaction. It can be used as a pre-autopsy screening, leading to a more extensive search for diseases not easily diagnosed, such as sepsis or ketoacidosis.

Utility of measuring serum levels of anti-PGL-I antibody, neopterin and C-reactive protein in monitoring leprosy patients during multi-drug treatment and reactions

Objective: To verify the validity of measuring the levels of Mycobacterium leprae‐specific anti‐phenolic glycolipid (PGL)‐I antibody, neopterin, a product of activated macrophages, and C‐reactive protein (CRP), an acute phase protein, in serial serum samples from patients for monitoring the leprosy spectrum and reactions during the course of multi‐drug treatment (MDT).Methods: Twenty‐five untreated leprosy patients, 15 multi‐bacillary (MB) and 10 paucibacillary (PB), participated. Eight patients developed reversal reaction and five developed erythema nodosum leprosum (ENL) during follow‐up. The bacterial index (BI) in slit‐skin smears was determined at diagnosis and blood samples collected by venipuncture at diagnosis and after 2, 4, 6 and 12 months of MDT. PGL‐I antibody and neopterin were measured by enzyme‐linked immunosorbent assay, whereas the CRP levels were measured by the latex agglutination method. Results: The levels of PGL‐I antibodies and neopterin were higher in the sera of MB than PB patients, which correlated with the patients’ BI. The serum levels of CRP did not differ significantly between the MB and PB patients. The serum levels of PGL‐I and neopterin were no higher in reactional patients than non‐reactional patients prone to such reactions. However, ENL patients had higher serum CRP levels than non‐reactional MB patients. The serum PGL‐I antibody levels declined significantly during MDT, in contrast to neopterin and CRP levels. Conclusion: Measuring the serum levels of PGL‐I antibodies and neopterin appeared to be useful in distinguishing MB from PB patients, whereas monitoring the levels of PGL‐I antibodies appeared to be useful in monitoring MB patients on MDT. Measuring serum CRP, although not useful in monitoring the patients, has limited significance in detecting ENL reactional patients

[Some acute phase proteins in children suffering from recurrent laryngeal papillomatosis]. / Wybrane bialka ostrej fazy u dzieci z nawracajacymi brodawczakami krtani.

INTRODUCTION: The aim of the study was to compare the character of inflammatory reaction in the groups of sick children, asymptomatic carriers of HPV and healthy children by quantitative and qualitative study of chosen acute phase proteins like CRP, AT, ACT. Profile of glycosylation of ACT was analysed. MATERIAL AND METHODS: The study group was 21 children treated in ENT Department of Pediatric Institute of the Karol Marcinkowski University for laryngeal papillomatosis (infected by HPV 6/11 in 100%) and the group of 22 selected asymptomatic carriers of HPV 6/11. The control group were 22 children in which the presence of HPV 6/11 DNA was excluded using PCR technique. Serum concentration of the APP was measured using immunoelectrophoresis technique according to Laurell. Qualitative study of the APP based on analysis of AGP and ACT microheterogeneity using crossed immuno-affinoelectrophoresis on agarose gel according to Bog-Hansen in Mackiewicz modification was carried out. RESULTS: The results were analysed with regard to: 1. the age of the first incident (ten children in whom the first symptoms occurred up to the second year of life, and eleven in whom the first symptoms were detected later; 2. severity of the disease course (seven children in whom four or more microsurgeries were performed within a year, and fourteen children in whom fever than four interventions were carried out). The decrease of ACT, AT levels in serum was observed. It was found that the ACT glycosylation profile is close to normal in sick children, what suggests the absence of inflammatory reaction stimulation. CONCLUSIONS: The results suggest that clinical infection of HPV is likely to be connected with discoordination of immunological reaction mechanism.

Reaction in leprosy: acute phase reactant response during and after remission.

Sera from 25 patients with type 1 (Lepra), upgrading and downgrading, and type 2 (erythema nodosum leprosum [ENL]) reactions were assayed, during the reaction and after its clinical remission, for changes in levels of alpha-1-antitrypsin (A1A) and C-reactive protein (CRP). The results were compared with those from normal healthy adults and patients of leprosy without history and/or clinical evidence of reaction. The A1A levels correlated better with changes in status of type 1 reaction; whereas CRP levels correlated well with alterations in type 2 reactions and were definitely superior to A1A in this situation for monitoring the course of these episodes.

Inappropriate responses to Mycobacterium leprae infections--C reactive protein in man and serum amyloid P in mice.

In a study of C-reactive protein (CRP) levels in the sera of 77 patients with leprosy, it was found that in the majority of newly diagnosed patients, the level was within the normal range for a healthy Malaysian population. Elevated levels did occur, but were usually found in patients with complications, and were more likely to occur in patients who had been receiving drug treatment for some time. This suggested that Mycobacterium leprae infection by itself does not stimulate CRP synthesis and could reflect a failure of synthesis by macrophages of interleukin-1, or related molecules. This was supported by the study of an analogous acute phase protein, serum amyloid P (SAP) in mice bearing M. leprae from human sources in their hind footpads. Such mice showed no significant difference in SAP levels from control mice.