Development and Validation of a Severity Scale for Leprosy Type 1 Reactions

Objectives

To develop a valid and reliable quantitative measure of leprosy Type 1 reactions.

Methods

A scale was developed from previous scales which had not been validated. The face and content validity were assessed following consultation with recognised experts in the field. The construct validity was determined by applying the scale to patients in Bangladesh and Brazil who had been diagnosed with leprosy Type 1 reaction. An expert categorized each patient''s reaction as mild or moderate or severe. Another worker applied the scale. This was done independently. In a subsequent stage of the study the agreement between two observers was assessed.

Results

The scale had good internal consistency demonstrated by a Cronbach''s alpha >0.8. Removal of three items from the original scale resulted in better discrimination between disease severity categories. Cut off points for Type 1 reaction severities were determined using Receiver Operating Characteristic curves. A mild Type 1 reaction is characterized using the final scale by a score of 4 or less. A moderate reaction is a score of between 4.5 and 8.5. A severe reaction is a score of 9 or more.

Conclusions

We have developed a valid and reliable tool for quantifying leprosy Type 1 reaction severity and believe this will be a useful tool in research of this condition, in observational and intervention studies, and in the comparison of clinical and laboratory parameters.     

Differential Dermal Expression of CCL17 and CCL18 in Tuberculoid and Lepromatous Leprosy

Background

Leprosy is characterized by polar clinical, histologic and immunological presentations. Previous immunologic studies of leprosy polarity were limited by the repertoire of cytokines known at the time.

Methodology

We used a candidate gene approach to measure mRNA levels in skin biopsies from leprosy lesions. mRNA from 24 chemokines and cytokines, and 6 immune cell type markers were measured from 85 Nepalese leprosy subjects. Selected findings were confirmed with immunohistochemistry.

Principal Results

Expression of three soluble mediators (CCL18, CCL17 and IL-10) and one macrophage cell type marker (CD14) was significantly elevated in lepromatous (CCL18, IL-10 and CD14) or tuberculoid (CCL17) lesions. Higher CCL18 protein expression by immunohistochemistry and a trend in increased serum CCL18 in lepromatous lesions was observed. No cytokines were associated with erythema nodosum leprosum or Type I reversal reaction following multiple comparison correction. Hierarchical clustering suggested that CCL18 was correlated with cell markers CD209 and CD14, while neither CCL17 nor CCL18 were highly correlated with classical TH1 and TH2 cytokines.

Conclusions

Our findings suggest that CCL17 and CCL18 dermal expression is associated with leprosy polarity.     

The prevalence of previously undiagnosed leprosy in the general population of northwest bangladesh

Background

The prevalence of previously undiagnosed leprosy (PPUL) in the general population was determined to estimate the background level of leprosy in the population and to compare this with registered prevalence and the known PPUL in different levels of contacts of leprosy patients.

Methodology and Principal Findings

Multistage cluster sampling including 20 clusters of 1,000 persons each in two districts with over 4 million population. Physical examination was performed on all individuals. The number of newly found leprosy cases among 17,862 people above 5 years of age from the cluster sample was 27 (19 SLPB, 8 PB2-5), giving a PPUL rate of 15.1 per 10,000.

Conclusions and Significance

PPUL in the general population is six times higher than the registered prevalence, but three times lower than that in the most distant subgroup of contacts (neighbour of neighbour and social contacts) of leprosy patients in the same area. Full village or neighbourhood surveys may be preferable to contact surveys where leprosy is highly endemic.     

The clinical importance of micrometastases within the lymphatic system in patients after total gastrectomy

Background

In spite of radical gastrectomy with resection of the lymphatic system, where no metastases are found during histopathological examination, about 30% of patients have relapse of the neoplastic process. This situation may be caused by micrometastases or isolated neoplastic cells in the lymphatic system which were not identified during a standard histopathological examination.

Aim

The aim of the study was to evaluate the clinical importance of micrometastases within the lymphatic system in patients with gastric cancer.

Materials and methods

A group of 20 patients treated for gastric cancer were subjected to retrospective analysis. Of all the patients who underwent surgery, a group with tumours classified as T1 or T2 was selected. No metastases within the lymphatic system were found in the standard evaluation – N0 mark. Paraffin-embedded blocks of lymph nodes were cut and new specimens were made, which were then stained again by means of immunohistochemistry. Antibodies against cytokeratin AE1/AE3 were used.

Results

A total of 319 lymph nodes were assessed in 20 patients in an H + E examination. After the immunohistochemical examination, micrometastases within the lymphatic system were found in 4 (20%) patients and isolated neoplastic cells in other 4 (20%) patients.

Conclusion

On the basis of numerous publications and our own material, we think that the presence of micrometastases may be related to a worse prognosis. The clinical importance of micrometastases within the lymphatic system in patients after total gastrectomy.     

Treatment of pure uterine sarcoma at the Institut Català D’Oncologia

Aim

The aim of this retrospective study was to investigate the clinical and histopathological characteristics of the disease and treatment outcome of patients with pure uterine sarcomas.

Background

Uterine sarcomas are especially rare tumours, comprising only 3–5% of uterine cancers. They are characterized by histopathological diversity, rapid clinical progression, and poor prognosis. Optimal management consists of complete surgical removal and adjuvant radiotherapy may improve the prognosis.

Materials and methods

All patients with pure uterine sarcoma histology treated at our centre, the Institut Català D’Oncologia in Barcelona Spain, between 2002 and 2010 were reviewed.

Results

Records of 17 patients treated at our hospital over an 8-year period were obtained. Nine patients (53%) had leiomyosarcoma, 7 (41%) had endometrial stromal sarcoma, and 1 patient had unclassified sarcoma. All patients were treated with external beam radiation after surgical excision. Mean age was 62 years (range, 51–69 years). Of the 17 patients, 13 (76%) presented with stage I disease, 2 (12%) were stage II, and 2 (12%) stage III. The overall actuarial 2-year survival estimate was 82.5%. Two patients experienced local relapse. The 2-year local control rate was 90%. A total of 5 patients experienced either local or metastatic relapse. The 2-year progression free survival rate was 58%.

Conclusion

In our experience, combined treatment (surgery and adjuvant radiation therapy) is effective with acceptable side effects. Larger and multicenter studies are needed to assess treatment outcome for pure uterine sarcoma histology.     

Evaluation of cellular phenotypes implicated in immunopathogenesis and monitoring immune reconstitution inflammatory syndrome in HIV/leprosy cases

Background

It is now evident that HAART-associated immunological improvement often leads to a variety of new clinical manifestations, collectively termed immune reconstitution inflammatory syndrome, or IRIS. This phenomenon has already been described in cases of HIV coinfection with Mycobacterium leprae, most of them belonging to the tuberculoid spectrum of leprosy disease, as observed in leprosy reversal reaction (RR). However, the events related to the pathogenesis of this association need to be clarified. This study investigated the immunological profile of HIV/leprosy patients, with special attention to the cellular activation status, to better understand the mechanisms related to IRIS/RR immunopathogenesis, identifying any potential biomarkers for IRIS/RR intercurrence.

Methods/Principal Findings

Eighty-five individuals were assessed in this study: HIV/leprosy and HIV-monoinfected patients, grouped according to HIV-viral load levels, leprosy patients without HIV coinfection, and healthy controls. Phenotypes were evaluated by flow cytometry for T cell subsets and immune differentiation/activation markers. As expected, absolute counts of the CD4+ and CD8+ T cells from the HIV-infected individuals changed in relation to those of the leprosy patients and controls. However, there were no significant differences among the groups, whether in the expression of cellular differentiation phenotypes or cellular activation, as reflected by the expression of CD38 and HLA-DR. Six HIV/leprosy patients identified as IRIS/RR were analyzed during IRIS/RR episodes and after prednisone treatment. These patients presented high cellular activation levels regarding the expression of CD38 in CD8+ cells T during IRIS/RR (median: 77,15%), dropping significantly (p<0,05) during post-IRIS/RR moments (median: 29,7%). Furthermore, an increase of cellular activation seems to occur prior to IRIS/RR.

Conclusion/Significance

These data suggest CD38 expression in CD8+ T cells interesting tool identifying HIV/leprosy individuals at risk for IRIS/RR. So, a comparative investigation to leprosy patients at RR should be conducted.     

Sterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis

Rationale

The sterilizing activity of the regimen used to treat multidrug resistant tuberculosis (MDR TB) has not been studied in a mouse model.

Objective and Methods

Swiss mice were intravenously inoculated with 6 log10 of Mycobacterium tuberculosis (TB) strain H37Rv, treated with second-line drug combinations with or without the diarylquinoline TMC207, and then followed without treatment for 3 more months to determine relapse rates (modified Cornell model).

Measurements

Bactericidal efficacy was assessed by quantitative lung colony-forming unit (CFU) counts. Sterilizing efficacy was assessed by measuring bacteriological relapse rates 3 months after the end of treatment.

Main Results

The relapse rate observed after 12 months treatment with the WHO recommended MDR TB regimen (amikacin, ethionamide, pyrazinamide and moxifloxacin) was equivalent to the relapse rate observed after 6 months treatment with the recommended drug susceptible TB regimen (rifampin, isoniazid and pyrazinamide). When TMC207 was added to this MDR TB regimen, the treatment duration needed to reach the same relapse rate dropped to 6 months. A similar relapse rate was also obtained with a 6-month completely oral regimen including TMC207, moxifloxacin and pyrazinamide but excluding both amikacin and ethionamide.

Conclusions

In this murine model the duration of the WHO MDR TB treatment could be reduced to 12 months instead of the recommended 18–24 months. The inclusion of TMC207 in the WHO MDR TB treatment regimen has the potential to further shorten the treatment duration and at the same time to simplify treatment by eliminating the need to include an injectable aminoglycoside.     

Association of laryngeal and nasopharyngeal tuberculosis: a case report

Introduction

To the best of our knowledge, the association of nasopharyngeal and laryngeal tuberculosis has never been described before in the literature. We report here a first observation.

Case presentation

We report the case of a 38-year-old Arab man who presented with an isolated hoarseness. Radiological and endoscopic examinations showed a thickening of the left lateral wall of his nasopharynx and the left vocal cord. Pathology revealed the diagnosis of tuberculosis of both localizations. He received a 6-month antituberculous chemotherapy with a satisfying uneventful evolution.

Conclusions

Tuberculosis should be considered in the differential diagnosis of soft tissue masses of the head and neck, particularly when the imaging findings and clinical presentation are atypical. The diagnosis of tuberculosis is mainly based on histopathological and/or bacteriological examination.     

Cost-effectiveness of a chemoprophylactic intervention with single dose rifampicin in contacts of new leprosy patients

Background

With 249,007 new leprosy patients detected globally in 2008, it remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR) for contacts as chemoprophylactic intervention in the control of leprosy.

Methods

We conducted a single centre, double blind, cluster randomised, placebo controlled trial in northwest Bangladesh between 2002 and 2007, including 21,711 close contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to close contacts, with follow-up for four years. The main outcome measure was the development of clinical leprosy. We assessed the cost effectiveness by calculating the incremental cost effectiveness ratio (ICER) between the standard multidrug therapy (MDT) program with the additional chemoprophylaxis intervention versus the standard MDT program only. The ICER was expressed in US dollars per prevented leprosy case.

Findings

Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total, $6,009 incremental cost was invested and 38 incremental leprosy cases were prevented, resulting in an ICER of $158 per one additional prevented leprosy case. It was the most cost-effective in neighbours of neighbours and social contacts (ICER $214), slightly less cost-effective in next door neighbours (ICER $497) and least cost-effective among household contacts (ICER $856).

Conclusion

Chemoprophylaxis with single dose rifampicin given to contacts of newly diagnosed leprosy patients is a cost-effective intervention strategy. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world.     

The Mortality Associated with Erythema Nodosum Leprosum in Ethiopia: A Retrospective Hospital-Based Study

Background

Erythema nodosum leprosum (ENL) is a debilitating multisystem disorder which complicates leprosy. It is characterised by fever, malaise and painful erythematous cutaneous nodules. ENL is often recurrent or chronic in nature and frequently severe. Patients often require prolonged treatment with high doses of oral corticosteroids. There are no data on the mortality associated with treated ENL.

Methodology

The notes of patients who were admitted, discharged, transferred to another facility or died with a diagnosis of leprosy or a leprosy-related complication for a five year period were reviewed.

Result/Discussion

414 individuals were identified from the ward database. 312 (75.4%) patient records were located and reviewed. Ninety-nine individuals had ENL and 145 had a Type 1 reaction. The median age of individuals with ENLwas 25 years. Eight patients with erythema nodosum leprosum died compared with two diagnosed with Type 1 reaction. This difference is statistically significant (p = 0.0168, Fisher''s Exact Test). There is a significant mortality and morbidity associated with ENL in this Ethiopian cohort. The adverse outcomes seen are largely attributable to the chronic administration of oral corticosteroids used to control the inflammatory and debilitating symptoms of the condition.     

Protein tyrosine phosphatase non-receptor type 22 gene polymorphism C1858T is not associated with leprosy in Azerbaijan,Northwest Iran

BACKGROUND:

Leprosy (Hansen''s disease) is a human chronic granulomatous infectious disease caused by Mycobacterium leprae. Several types of study support a role for host genetics in susceptibility to leprosy. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an intracellular lymphoid protein tyrosine phosphatase that has been shown to play a negative regulatory role in T-cell activation.

AIMS:

The aim of the present study was to find out associating the PTPN22 C1858T (R620W) polymorphism and leprosy in the Azeri population from Northwest Iran.

MATERIALS AND METHODS:

A total of 153 treated leprosy patients and 197 healthy and ethnic matched controls entered this study. We used restriction fragment length polymorphism method to type PTPN22 C1858T polymorphism.

RESULTS:

There was no significant difference in distribution of genotype and allele frequencies of PTPN22 C1858T polymorphism between leprosy patients and controls (P = 0.641 and 0.645; respectively). Moreover, there was no significant association between different clinical findings (karnofsky performance status score, clinical forms and manifestations of leprosy) and PTPN22 C1858T polymorphism. Data showed a low frequency of the minor (T) allele by 2.3% in leprosy and 1.5% in healthy individuals.

CONCLUSIONS:

The PTPN22 C1858T (R620W) is not relevant in susceptibility to leprosy in the Azeri population of Northwest Iran.     

Use of short tandem repeat sequences to study Mycobacterium leprae in leprosy patients in Malawi and India

Background

Inadequate understanding of the transmission of Mycobacterium leprae makes it difficult to predict the impact of leprosy control interventions. Genotypic tests that allow tracking of individual bacterial strains would strengthen epidemiological studies and contribute to our understanding of the disease.

Methodology/Principal Findings

Genotyping assays based on variation in the copy number of short tandem repeat sequences were applied to biopsies collected in population-based epidemiological studies of leprosy in northern Malawi, and from members of multi-case households in Hyderabad, India. In the Malawi series, considerable genotypic variability was observed between patients, and also within patients, when isolates were collected at different times or from different tissues. Less within-patient variability was observed when isolates were collected from similar tissues at the same time. Less genotypic variability was noted amongst the closely related Indian patients than in the Malawi series.

Conclusions/Significance

Lineages of M. leprae undergo changes in their pattern of short tandem repeat sequences over time. Genetic divergence is particularly likely between bacilli inhabiting different (e.g., skin and nerve) tissues. Such variability makes short tandem repeat sequences unsuitable as a general tool for population-based strain typing of M. leprae, or for distinguishing relapse from reinfection. Careful use of these markers may provide insights into the development of disease within individuals and for tracking of short transmission chains.     

Month 2 Culture Status and Treatment Duration as Predictors of Tuberculosis Relapse Risk in a Meta-Regression Model

Background

New drugs and regimens with the potential to transform tuberculosis treatment are presently in early stage clinical trials.

Objective

The goal of the present study was to infer the required duration of these treatments.

Method

A meta-regression model was developed to predict relapse risk using treatment duration and month 2 sputum culture positive rate as predictors, based on published historical data from 24 studies describing 58 regimens in 7793 patients. Regimens in which rifampin was administered for the first 2 months but not subsequently were excluded. The model treated study as a random effect.

Results

The model predicted that new regimens of 4 or 5 months duration with rates of culture positivity after 2 months of 1% or 3%, would yield relapse rates of 4.0% or 4.1%, respectively. In both cases, the upper limit of the 2-sided 80% prediction interval for relapse for a hypothetical trial with 680 subjects per arm was <10%. Analysis using this model of published month 2 data for moxifloxacin-containing regimens indicated they would result in relapse rates similar to standard therapy only if administered for ≥5 months.

Conclusions

This model is proposed to inform the required duration of treatment of new TB regimens, potentially hastening their accelerated approval by several years.     

Epitope Analysis of Anti-Myeloperoxidase Antibodies in Patients with ANCA-Associated Vasculitis

Objective

Increasing evidences have suggested the pathogenic role of anti-neutrophil cytoplasmic antibodies (ANCA) directing myeloperoxidase (MPO) in ANCA-associated vasculitis (AAV). The current study aimed to analyze the association between the linear epitopes of MPO-ANCA and clinicopathological features of patients with AAV.

Methods

Six recombinant linear fragments, covering the whole length amino acid sequence of a single chain of MPO, were produced from E.coli. Sera from 77 patients with AAV were collected at presentation. 13 out of the 77 patients had co-existence of serum anti-GBM antibodies. Ten patients also had sequential sera during follow up. The epitope specificities were detected by enzyme-linked immunosorbent assay using the recombinant fragments as solid phase ligands.

Results

Sera from 45 of the 77 (58.4%) patients with AAV showed a positive reaction to one or more linear fragments of the MPO chain. The Birmingham Vasculitis Activity Scores and the sera creatinine were significantly higher in patients with positive binding to the light chain fragment than that in patients without the binding. The epitopes recognized by MPO-ANCA from patients with co-existence of serum anti-GBM antibodies were mainly located in the N-terminus of the heavy chain. In 5 out of the 6 patients, whose sera in relapse recognize linear fragments, the reactivity to linear fragments in relapse was similar to that of initial onset.

Conclusion

The epitope specificities of MPO-ANCA were associated with disease activity and some clinicopathological features in patients with ANCA-associated vasculitis.     

Neuropathic pain and psychological morbidity in patients with treated leprosy: a cross-sectional prevalence study in Mumbai

Background

Neuropathic pain has been little studied in leprosy. We assessed the prevalence and clinical characteristics of neuropathic pain and the validity of the Douleur Neuropathique 4 questionnaire as a screening tool for neuropathic pain in patients with treated leprosy. The association of neuropathic pain with psychological morbidity was also evaluated.

Methodology/Principal Findings

Adult patients who had completed multi-drug therapy for leprosy were recruited from several Bombay Leprosy Project clinics. Clinical neurological examination, assessment of leprosy affected skin and nerves and pain evaluation were performed for all patients. Patients completed the Douleur Neuropathique 4 and the 12-item General Health Questionnaire to identify neuropathic pain and psychological morbidity.

Conclusions/Significance

One hundred and one patients were recruited, and 22 (21.8%) had neuropathic pain. The main sensory symptoms were numbness (86.4%), tingling (68.2%), hypoesthesia to touch (81.2%) and pinprick (72.7%). Neuropathic pain was associated with nerve enlargement and tenderness, painful skin lesions and with psychological morbidity. The Douleur Neuropathique 4 had a sensitivity of 100% and specificity of 92% in diagnosing neuropathic pain. The Douleur Neuropathique 4 is a simple tool for the screening of neuropathic pain in leprosy patients. Psychological morbidity was detected in 15% of the patients and 41% of the patients with neuropathic pain had psychological morbidity.     

Impact of PGL-I seropositivity on the protective effect of BCG vaccination among leprosy contacts: a cohort study

Background

Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I) antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by Bacille Calmette Guerin (BCG) vaccination after index case diagnosis.

Methodology/Principal Findings

Leprosy contacts were examined as part of the surveillance programme of the Oswaldo Cruz Institute Leprosy Outpatient Clinic in Rio de Janeiro. Demographic, social, epidemiological and clinical data were collected. The presence of IgM antibodies to PGL-I in sera and BCG vaccination status at the time of index case diagnosis were evaluated in 2,135 contacts. During follow-up, 60 (2.8%; 60/2,135) leprosy cases were diagnosed: 41 among the 1,793 PGL-I-negative contacts and 19 among the 342 PGL-I-positive contacts. Among PGL-I-positive contacts, BCG vaccination after index case diagnosis increased the adjusted rate of developing clinical manifestations of leprosy (Adjusted Rate Ratio (aRR) = 4.1; 95% CI: 1.8–8.2) compared with the PGL-I-positive unvaccinated contacts (aRR = 3.2; 95% CI: 1.2–8.1). The incidence density was highest during the first year of follow-up for the PGL-I-positive vaccinated contacts. However, all of those contacts developed PB leprosy, whereas most MB cases (4/6) occurred in PGL-I-positive unvaccinated contacts.

Conclusion

Contact examination combined with PGL-I testing and BCG vaccination remain important strategies for leprosy control. The finding that rates of leprosy cases were highest among seropositive contacts justifies targeting this specific group for close monitoring. Furthermore, it is recommended that PGL-I-positive contacts and contacts with a high familial bacteriological index, regardless of serological response, should be monitored. This group could be considered as a target for chemoprophylaxis.     

High-Resolution Sonography: A New Technique to Detect Nerve Damage in Leprosy

Background

Leprosy is the most common treatable peripheral nerve disorder worldwide with periods of acute neuritis leading to functional impairment of limbs, ulcer formation and stigmatizing deformities. Since the hallmarks of leprosy are nerve enlargement and inflammation, we used high-resolution sonography (US) and color Doppler (CD) imaging to demonstrate nerve enlargement and inflammation.

Methology/Principal Findings

We performed bilateral US of the ulnar (UN), median (MN), lateral popliteal (LP) and posterior tibial (PT) nerves in 20 leprosy patients and compared this with the clinical findings in these patients and with the sonographic findings in 30 healthy Indian controls.The nerves were significantly thicker in the leprosy patients as compared to healthy controls (p<0.0001 for each nerve). The two patients without nerve enlargements did not have a type 1 or type 2 reaction or signs of neuritis. The kappa for clinical palpation and nerve enlargement by sonography was 0.30 for all examined nerves (0.32 for UN, 0.41 for PN and 0.13 for LP). Increased neural vascularity by CD imaging was present in 39 of 152 examined nerves (26%). Increased vascularity was observed in multiple nerves in 6 of 12 patients with type 1 reaction and in 3 of 4 patients with type 2 reaction. Significant correlation was observed between clinical parameters of grade of thickening, sensory loss and muscle weakness and US abnormalities of nerve echotexture, endoneural flow and cross-sectional area (p<0.001).

Conclusions/Significance

We conclude that clinical examination of enlarged nerves in leprosy patients is subjective and inaccurate, whereas sonography provides an objective measure of nerve damage by showing increased vascularity, distorted echotexture and enlargement. This damage is sonographically more extensive and includes more nerves than clinically expected.     

Baseline MxA mRNA Expression Predicts Interferon Beta Response in Multiple Sclerosis Patients

Background

Myxovirus resistance protein A (MxA) is a molecule induced after interferon-beta injection, mostly used to evaluate its bioactivity. There is little available data on clinical utility of baseline MxA mRNA status. The objective of the study is to investigate whether baseline MxA mRNA expression can predict relapse and disease progression in multiple sclerosis patients treated with interferon-beta.

Methods

Baseline blood samples were obtained before the first interferon-beta dose was administered to evaluate MxA mRNA expression using real-time polymerase chain reaction (PCR). Demographic and clinical variables were prospectively recorded to define treatment responder and non responder groups.

Results

104 patients were included in the study. Baseline MxA mRNA expression was significantly lower in the group of patients who met the definition of responders (1.07 vs 1.95, Student t test, p<0.0001). A threshold of 1.096 was established using Receiver Operating Characteristic analysis to differentiate between responders and non-responders (sensitivity 73.9%, specificity 69.0%). Survival analysis using this threshold showed that time to next relapse (p<0.0001) and to EDSS progression (p = 0.01) were significantly higher in patients with lower MxA titers.

Conclusion

The results suggest that baseline MxA mRNA levels may be useful for predicting whether multiple sclerosis patients will respond or not to interferon-beta treatment.     

A simple scoring system to differentiate between relapse and re-infection in patients with recurrent melioidosis

Background

Melioidosis is an important cause of morbidity and mortality in East Asia. Recurrent melioidosis occurs in around 10% of patients following treatment either because of relapse with the same strain or re-infection with a new strain of Burkholderia pseudomallei. Distinguishing between the two is important but requires bacterial genotyping. The aim of this study was to develop a simple scoring system to distinguish re-infection from relapse.

Methods

In a prospective study of 2,804 consecutive adult patients with melioidosis presenting to Sappasithiprasong Hospital, NE Thailand, between1986 and 2005, there were 141 patients with recurrent melioidosis with paired strains available for genotyping. Of these, 92 patients had relapse and 49 patients had re-infection. Variables associated with relapse or re-infection were identified by multivariable logistic regression and used to develop a predictive model. Performance of the scoring system was quantified with respect to discrimination (area under receiver operating characteristic curves, AUC) and categorization (graphically). Bootstrap resampling was used to internally validate the predictors and adjust for over-optimism.

Findings

Duration of oral antimicrobial treatment, interval between the primary episode and recurrence, season, and renal function at recurrence were independent predictors of relapse or re-infection. A score of <5 correctly identified relapse in 76 of 89 patients (85%), whereas a score ≥5 correctly identified re-infection in 36 of 52 patients (69%). The scoring index had good discriminative power, with a bootstrap bias-corrected AUC of 0.80 (95%CI: 0.73–0.87).

Conclusions

A simple scoring index to predict the cause of recurrent melioidosis has been developed to provide important bedside information where rapid bacterial genotyping is unavailable.