Standard Multidrug Therapy Research Articles

Primary Mandibular Tuberculous Osteomyelitis Mimicking Ameloblastoma: A Case Report and Literature Review of Mandibular Tuberculous Osteomyelitis.

Primary tuberculous osteomyelitis involving the mandible represents less than 2% of skeletal locations. In this paper, we report a case of mandibular tuberculosis (TB) detected after histopathological analysis of the surgically resected specimen during surgical management of a suspected case of ameloblastoma. A 14-year-old male patient presented to us with history of right-sided chin swelling. The clinical examination revealed a swelling, involving right body and parasymphysis of mandible, measuring approximately 6 cm in length and 2 cm in width, extending from right lateral incisor till the first molar. Radiological scans revealed a large multiloculated osteolytic expansive lesion measuring 52 × 20 × 18 mm. Excision of the lesion was performed and reconstruction was done with iliac bone grafting. The histopathological findings revealed a granulomatous lesion, suggestive of tuberculous osteomyelitis. The patient was successfully treated with standard multidrug therapy. One year after completion of therapy, there were no signs of recurrence. Primary mandibular TB is an extremely rare entity. Its clinical presentation is not specific. Radiologically, TB has no characteristic appearance. The positive diagnosis is based on histology. Primary mandibular TB is rare and should be kept among differential diagnoses in susceptible population and in endemic areas.

Development of a multivariate predictive model for dapsone adverse drug events in people with leprosy under standard WHO multidrug therapy.

The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.

Scenarios warranting modified treatment regimens in leprosy: A 5-year retrospective study from a tertiary care center

Objectives: To study the scenarios warranting modified treatment regimens in leprosy. Materials and Methods: A 5-year retrospective study was carried out in a tertiary care center by analyzing the data collected from national leprosy eradication program (NLEP) records. Results: During the 5-year study period, 171 patients received treatment for leprosy from our center. Thirtyone patients (31/171, 18.1%) required substitution of standard multidrug therapy (MDT) with alternate drugs or required alternate treatment regimens. The patients who required modified treatment included 18 men (18/31, 58.1%) and 13 women (41.9%). Male/female ratio was 1.4:1. Indications for treatment modification were adverse drug reactions to standard MDT (ADR) (21/31, 67.7%) and lack of response to standard MDT (10/31, 32.3%). The most common scenario that warranted a modification of standard MDT was dapsone-induced hemolysis (12/31, 38.7%). Seven (7/31, 22.6%) and two (2/31, 6.5%) patients needed a change in treatment due to drug-induced hepatitis and drug-induced maculopapular rash, respectively. Limitations: Retrospective study design, study conducted in single tertiary referral center and small sample size were the limitations. Conclusion: Nearly one-fifth of patients with leprosy required modifications in standard MDT. The most common indication (in two-third of patients who needed a modified treatment) for modification of treatment regimen was adverse drug reactions.

Effectivity of Uniform Multidrug Therapy on the Success of Paucibacillary and Multibacillary Leprosy Treatment

Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) that involves the integumentary and peripheral nervous system, causing neuropathy, deformity, and disability. Early detection and appropriate treatment are the ways to break the chain of transmission and prevent disability in leprosy patients. The first line of treatment for leprosy is the standard Multidrug Therapy (MDT) regiment consisting of rifampicin, dapsone, and clofazimine. Standard MDT treatment is given based on the leprosy classification of paucibacillary (PB) and multibacillary (MB). The utilization of the standard MDT regiment has some limitations, particularly where there is a limited supporting test facility, causing difficulty in determining the leprosy classification accurately. An alternative regiment proposed to substitute the standard MDT is the Uniform-MDT (U-MDT). Several studies have been conducted on the use of U-MDT and have produced promising results for the treatment of PB and MB leprosy.

Evaluating the Rate and Timing of Reactions Among Patients With Hansen’s Disease

Background Immunologic reactions are a major complication of Hansen’s disease, also known as leprosy. To minimize reactions, clofazimine is added to multidrug therapy for its anti-inflammatory effect. Minocycline is an alternative antileprosy medication that has evidence to suggest it also has anti-inflammatory properties. Objective The aim of this study was to evaluate whether there is a difference in the frequency of reactional episodes and time of onset while receiving minocycline for Hansen's disease compared with multidrug therapy. Methods This study used an observational design comparing two independent groups. Results No differences were found between reaction occurrence and time to onset in patients who received either alternative therapy with minocycline or standard multidrug therapy treatment with clofazimine. Logistic regression indicated a significant association between borderline tuberculoid and reactions (χ2[1] = 3.898, p = .048). Patients with borderline tuberculoid were 68% less likely to develop reactions (Type 1 or 2) than other types of Hansen's disease while accounting for treatment, age, and race (OR = 0.320, 95% CI [0.103, 0.992]). Conclusion Although there was no significant difference in reaction rate between treatment groups, these findings indicate the clinical form borderline tuberculoid is a significant negative predictor for reactions. However, sample size limited the ability to determine significance based on reaction type.

Hubungan Asupan Vitamin D Dan Selenium Dengan Indeks Bakteriologi Penderita Kusta Tipe MB (Multibacillary) : Systematic Literature Review

Background : As one of the infectious diseases that have a high prevalence until now, leprosy is a chronic transmission disease caused by infection with Mycobacterium Leprae. Apart from the standard MDT (Multidrug Therapy), nutritional support is a crucial component to restrict further infection severity. Vitamin D and selenium play essential roles as the primary defence against susceptibility. Methods : The systematic literature review was conducted using three international databases : PubMed, ResearchGate, and DOAJ, which were published between 2010 – 2020 using English or Indonesian. A total of 8 articles (2 articles identifying the correlation of selenium with leprosy, and 6 articles identifying the correlation of vitamin D with leprosy) using cross- sectional analytic and case-control analytic studies were included in this review. Results : The average serum levels of vitamin D and selenium in leprosy patients were lower than in healthy controls. This case was also found in Multibacillary leprosy patients compared to Paucibacillary leprosy patients. This serum levels can affect the bacteriological index, which is the higher the serum levels, the lower the bacteriological index. Disscusion : Serum vitamin D and selenium levels are affected by vitamin D and selenium intake, which can lead to a reduction in bacteriological index across all multibacillary leprosy patients. There is a negative correlation between vitamin D, selenium, and bacteriological index in patients with MB (Multibacillary) leprosy.Keywords:Leprosy, Vitamin D, Selenium, Bacteriological Index

The Role of Lipid and the Benefit of Statin in Augmenting Rifampicin Effectivity for a Better Leprosy Treatment

Although leprosy remains as a serious disease of the skin and nervous system, the current treatment is still lacking in its effectiveness. This literature review will explore the association of lipid and leprosy, as well as the potential of statin and other lipid-lowering agents as adjunctive drugs to combat leprosy. Articles were searched through the PubMed, EBSCOhost, and Google Scholar with the keywords: immunomodulation, lipid-body, lipids, leprosy, Mycobacterium leprae, pathogenesis, rifampin or rifampicin, and statins. A manual searching is also carried out to find an additional relevant information to make this literature review more comprehensive. The literatures showed that lipids are highly correlated with leprosy through alterations in serum lipid profile, metabolism, pathogenesis, and producing oxidative stress. Statins can diminish lipid utilization in the pathogenesis of leprosy and show a mycobactericidal effect by increasing the effectiveness of rifampicin and recover the function of macrophages. In addition, Statins have anti-inflammatory properties which may aid in preventing type I and II reactions in leprosy. Standard multidrug therapy might reduce the efficacy of statins, but the effect is not clinically significant. The statin dose-response curve also allows therapeutic response to be achieved with minimal dose. The various pleiotropic effects of statins make it a potential adjunct to standard treatment for leprosy in the future.

Ofloxacin-Containing Multidrug Therapy in Ambulatory Leprosy Patients: A Case Series.

Standard dapsone and clofazimine-containing multidrug therapy (MDT) for leprosy is limited by drug tolerability, which poses treatment adherence barriers. Although ofloxacin-based regimens are promising alternatives, current efficacy and safety data are limited, particularly outside of endemic areas. We evaluated treatment outcomes in patients with leprosy receiving ofloxacin-containing MDT (OMDT) at our center. We performed a retrospective chart review of patients treated for leprosy at our center over an 8-year period (2011-2019). Primary outcomes evaluated were clinical cure rate, occurrence of leprosy reactions, antibiotic-related adverse events, and treatment adherence. Analyses were descriptive; however, data were stratified by age, sex, spectrum of disease, region of origin, and treatment regimen, and odds ratios were reported to assess associations with adverse outcomes. Over the enrolment period, 26 patients were treated with OMDT (n = 19 multibacillary, n = 7 paucibacillary), and none were treated with clofazimine-based standard MDT. At the time of analysis, 23 patients (88%) had completed their course of treatment, and all were clinically cured, while 3 (12%) were still on treatment. Eighteen patients (69%) experienced either ENL (n = 7, 27%), type 1 reactions (n = 7, 27%), or both (n = 4, 15%). No patients stopped ofloxacin due to adverse drug effects, and there were no cases of allergic hypersensitivity, tendinopathy or rupture, or C. difficile colitis. We demonstrate a high cure rate and tolerability of OMDT in this small case series over an 8-year period, suggesting its viability as an alternative to standard clofazimine-containing MDT.

Evidence for Mycobacterium leprae Drug Resistance in a Large Cohort of Leprous Neuropathy Patients from India.

Resistance to anti-leprosy drugs is on the rise. Several studies have documented resistance to rifampicin, dapsone, and ofloxacin in patients with leprosy. We looked for point mutations within the folP1, rpoB, and gyrA gene regions of the Mycobacterium leprae genome predominantly in the neural form of leprosy. DNA samples from 77 nerve tissue samples were polymerase chain reaction (PCR)-amplified for M leprae DNA and sequenced for drug resistance-determining regions of genes rpoB, folP1, and gyrA. The mean age at presentation and onset was 38.2 ± 13.4 (range 14-71) years and 34.9 ± 12.6 years (range 10-63) years, respectively. The majority had borderline tuberculoid leprosy (53 [68.8%]). Mutations associated with resistance were identified in 6/77 (7.8%) specimens. Mutations seen were those associated with resistance to rifampicin, ofloxacin, and dapsone. All the six patients were drug-naive. The clinical and pathological manifestations in this group did not differ from the drug-sensitive group. This study highlights the occurrence of resistance to the standard multidrug therapy and ofloxacin in leprosy. Among the entire cohort, 1/77 (1.3%) showed resistance to rifampicin, 2/77 (2.6%) to dapsone, and 5/77 (6.4%) to ofloxacin. Six new patients showing infection by mutant strains indicated the emergence of primary resistance. Resistance to ofloxacin could be due to frequent use of quinolones for many bacterial infections. The results of the study indicate the need for development of a robust and strict surveillance system for detecting drug resistance in leprosy in India.

Utility and limitations of serodiagnostic tests in monitoring the response to treatment of leprosy patients

Simple measures that can facilitate early recognition of leprosy complications are still lacking. We therefore evaluated a lateral flow-based rapid diagnostic test and fast enzyme-linked immunosorbent assay measuring anti-LID-NDO antibody responses among leprosy cases in Cebu, Philippines. Responses were measured at diagnosis, then during and after the provision of standard multidrug therapy. Our data indicate that both platforms are highly sensitive tools for the primary diagnosis of, in particular, multibacillary leprosy. A gradual, quantifiable decline in both magnitude of response and percent positive responders was observed during and after treatment. As a group, patients that developed erythema nodosum leprosum (ENL) had a significantly higher response at diagnosis than patients that either developed reversal reactions or did not develop reactions. Although higher initial anti-NDO-LID responses were a risk factor for ENL, neither platform, however, could reliably predict the time of emergence of reactional episodes.

Evaluation of Prospective HLA-B*13:01 Screening to Prevent Dapsone Hypersensitivity Syndrome in Patients With Leprosy

Dapsone hypersensitivity syndrome (DHS) is the most serious adverse reaction associated with dapsone administration and one of the major causes of death in patients with leprosy, whose standard treatment includes multidrug therapy (MDT) with dapsone, rifampicin, and clofazimine. Although the HLA-B*13:01 polymorphism has been identified as the genetic determinant of DHS in the Chinese population, no studies to date have been done to evaluate whether prospective HLA-B*13:01 screening could prevent DHS by identifying patients who should not receive dapsone. To evaluate the clinical use of prospective HLA-B*13:01 screening for reduction of the incidence of DHS by excluding dapsone from the treatment for patients with HLA-B*13:01-positive leprosy. A prospective cohort study was conducted from February 15, 2015, to April 30, 2018, in 21 provinces throughout China. A total of 1539 patients with newly diagnosed leprosy were enrolled who had not received dapsone previously. After excluding patients who had a history of allergy to sulfones or glucose-6-phosphate dehydrogenase deficiency, 1512 individuals underwent HLA-B*13:01 genotyping. All of the patients were followed up weekly for the first 8 weeks after treatment to monitor for adverse events. Patients who were HLA-B*13:01 carriers were instructed to eliminate dapsone from their treatment regimens, and noncarrier patients received standard MDT. The primary outcome was the incidence of DHS. The historical incidence rate of DHS (1.0%) was used as a control. Among 1512 patients (1026 [67.9%] men, 486 [32.1%] women; mean [SD] age, 43.1 [16.2] years), 261 (17.3%) were identified as carriers of the HLA-B*13:01 allele. A total of 714 adverse events in 384 patients were observed during the follow-up period. Dapsone hypersensitivity syndrome did not develop in any of the 1251 patients who were HLA-B*13:01-negative who received dapsone, while approximately 13 patients would be expected to experience DHS, based on the historical incidence rate of 1.0% per year (P = 2.05 × 10-5). No significant correlation was found between other adverse events, including dermatologic or other events, and HLA-B*13:01 status. Prospective HLA-B*13:01 screening and subsequent elimination of dapsone from MDT for patients with HLA-B*13:01-positive leprosy may significantly reduce the incidence of DHS in the Chinese population.

Ribonucleotide reductase as a drug target against drug resistance Mycobacterium leprae: A molecular docking study

Leprosy is a chronic infection of skin and nerve caused by Mycobacterium leprae. The treatment is based on standard multi drug therapy consisting of dapsone, rifampicin and clofazamine. The use of rifampicin alone or with dapsone led to the emergence of rifampicin-resistant Mycobacterium leprae strains. The emergence of drug-resistant leprosy put a hurdle in the leprosy eradication programme. The present study aimed to predict the molecular model of ribonucleotide reductase (RNR), the enzyme responsible for biosynthesis of nucleotides, to screen new drugs for treatment of drug-resistant leprosy. The study was conducted by retrieving RNR of M. leprae from GenBank. A molecular 3D model of M. leprae was predicted using homology modelling and validated. A total of 325 characters were included in the analysis. The predicted 3D model of RNR showed that the ϕ and φ angles of 251 (96.9%) residues were positioned in the most favoured regions. It was also conferred that 18 α-helices, 6 β turns, 2 γ turns and 48 helix–helix interactions contributed to the predicted 3D structure. Virtual screening of Food and Drug Administration approved drug molecules recovered 1829 drugs of which three molecules, viz., lincomycin, novobiocin and telithromycin, were taken for the docking study. It was observed that the selected drug molecules had a strong affinity towards the modelled protein RNR. This was evident from the binding energy of the drug molecules towards the modelled protein RNR (−6.10, −6.25 and −7.10). Three FDA-approved drugs, viz., lincomycin, novobiocin and telithromycin, could be taken for further clinical studies to find their efficacy against drug resistant leprosy.

History of chemotherapy of leprosy

Chemotherapy of leprosy over the past 70 years has passed through several phases, from sulfones, to clofazimine, and to highly bactericidal drugs like rifampicin. The use particularly of the more potent drugs in effective combinations and the development of standard multidrug therapy regimens have made a huge difference in the successful treatment of leprosy as well as in reducing tremendously the prevalence of leprosy globally. A major contributing factor to development of better drugs and drug combinations has been the introduction of the mouse footpad model to evaluate the in vivo activity of drugs against Mycobacterium leprae. The World Health Organization has recommended multidrug therapy, which has been used to treat more than 15 million patients in the last 30 years and has set an excellent record with regard to its very high rate of cure, very low occurrence of relapse, and very rare occurrence of drug resistance.

Postoperative Monotherapy with Piperacillin-Tazobactam versus Multidrug Therapy with Cefotaxime and Metronidazole for Perforated Appendicitis in Children: A Case-Control Study

Purpose: Recent data suggest that monotherapy with a broad-spectrum antibiotic may be as efficacious as, and potentially less costly than, standard multi-drug therapy. We compared mono-therapy with intravenous piperacillin-tazobactam (PT) with multi-drug therapy with cefotaxime and metronidazole (CM) in aspect of postoperative complications and hospital stay. Methods: We reviewed the hospital records and medical costs of the pediatric patients who were managed for perforated appendicitis between April 2013 and May 2014 retrospectively. Results: Forty-six patients with laparoscopic appendectomy for perforated appendicitis were included in our study. PT group was 20 and CM group was 26 patients. On admission, there were no significance in sex distribution, duration of symptoms, leukocyte count, and CRP levels. At postoperative third, fifth, and seventh day of each regimen, PT group have no statistical difference with CM group in leukocyte count, percentage of neutrophil, and CRP. There was no difference in abscess formation rate, wound infections, and hospital stay between two groups. There was only one patient who was readmitted with elevation of CRP and leukocyte count in CM group. Conclusion: Daily dosing with the mono-therapy of PT offers as efficient as multi-drug therapy of CM. To evaluate the efficacy of broad-spectrum antibiotics monotherapy in perforated appendicitis children, the cohort included more patients should be needed.

The beneficial effects of adjunctive recombinant human interleukin-2 for multidrug resistant tuberculosis.

IntroductionMultidrug-resistant tuberculosis (MDR-TB) is a hard-to-treat disease with a poor outcome of chemotherapy. In the present study, the efficacy and safety of recombinant human interleukin-2 (rhIL-2) were investigated in patients with MDR-TB.Material and methodsFifty culture-confirmed patients with MDR-TB were included. Twenty-five patients were randomly assigned to the trial group (injection of 500 000 IU of rhIL-2 once every other day at the first, third, fifth and seventh months in addition to standard multidrug therapy) and another 25 patients to the control group with standard multidrug therapy. All patients were monitored clinically, and T-cell subsets were analyzed by flow cytometry.ResultsThe rates of sputum negative conversion and X-ray resolution in the trial group were higher than those of the control, and the improvements were significant by completion of treatment. In addition, CD4+CD25+ T cells in the controls rose gradually during treatment. The levels at the end of the seventh month were significantly higher than before, which were also significantly different when compared with those from the trial group at the same time. However, there were no such changes associated with treatment in the trial group. No significant differences appeared in other T cell subsets.ConclusionsExogenous IL-2 in the present regimen improves immunity status. Adjunctive immunotherapy with a long period of rhIL-2 is a promising treatment modality for MDR-TB.

Leprosy: a review of laboratory and therapeutic aspects - Part 2

Leprosy is a chronic infectious condition caused by Mycobacterium leprae(M. leprae). It is endemic in many regions of the world and a public health problem in Brazil. Additionally, it presents a wide spectrum of clinical manifestations, which are dependent on the interaction between M. leprae and host, and are related to the degree of immunity to the bacillus. The diagnosis of this disease is a clinical one. However, in some situations laboratory exams are necessary to confirm the diagnosis of leprosy or classify its clinical form. This article aims to update dermatologists on leprosy, through a review of complementary laboratory techniques that can be employed for the diagnosis of leprosy, including Mitsuda intradermal reaction, skin smear microscopy, histopathology, serology, immunohistochemistry, polymerase chain reaction, imaging tests, electromyography, and blood tests. It also aims to explain standard multidrug therapy regimens, the treatment of reactions and resistant cases, immunotherapy with bacillus Calmette-Guérin (BCG) vaccine and chemoprophylaxis.

¿Es la resistencia de Mycobacterium leprae a los medicamentos un verdadero motivo de preocupación? Primera aproximación a la vigilancia molecular de pacientes colombianos multibacilares con tratamiento previo para lepra y sin él

There is no information in Colombia on Mycobacterium leprae primary and secondary drug resistance in regards to the WHO-multidrug therapy regime. On the other hand, public health authorities around the world have issued various recommendations, one of which prompts for the immediate organization of resistance surveillance through simple molecular methods.To determine the prevalence of Mycobacterium leprae drug resistance to rifampicin, ofloxacin and dapsone in untreated and previously treated patients at the Centro Dermatológico Federico Lleras Acosta during the 1985-2004 period.We conducted a retrospective study which included multibacillary patient biopsies through elective sampling: 381 of them from new patients and 560 from previously treated patients. Using a microtome, we obtained six slides from each skin biopsy preserved in paraffin, and we extracted M. leprae DNA. We amplified three molecular targets through PCR and obtained the patterns of drug resistance to dapsone, rifampicin and ofloxacin by reverse hybridization. Finally, we collected epidemiological, clinical and demographical data for analyses.From 941 samples under study, 4.14% of them were resistant to one or more drugs, and 5.77 and 3.04% had resistant genotypes in new and previously treated patients, respectively. Total resistance for each drug was 0.43% for dapsone, 3.19% for rifampicin and 1.17% for ofloxacin. We found statistically significant differences for rifampicin and for the total population when comparing the results from untreated versus previously treated patients. Two thirds of the resistant samples were resistant to rifampicin alone or combined.The standard multidrug therapy schemes continue being effective for leprosy cases; however, it is necessary to guarantee adherence and regularity. Surveillance to drug resistance in new and previously treated leprosy cases should be established.

Is drug-resistant Mycobacterium leprae a real cause for concern?: First approach to molecular monitoring of multibacillary Colombian patients with and without previous leprosy treatment.

There is no information in Colombia on Mycobacterium leprae primary and secondary drug resistance in regards to the WHO-multidrug therapy regime. On the other hand, public health authorities around the world have issued various recommendations, one of which prompts for the immediate organization of resistance surveillance through simple molecular methods. To determine the prevalence of Mycobacterium leprae drug resistance to rifampicin, ofloxacin and dapsone in untreated and previously treated patients at the Centro Dermatológico Federico Lleras Acosta during the 1985-2004 period. We conducted a retrospective study which included multibacillary patient biopsies through elective sampling: 381 of them from new patients and 560 from previously treated patients. Using a microtome, we obtained six slides from each skin biopsy preserved in paraffin, and we extracted M. leprae DNA. We amplified three molecular targets through PCR and obtained the patterns of drug resistance to dapsone, rifampicin and ofloxacin by reverse hybridization. Finally, we collected epidemiological, clinical and demographical data for analyses. From 941 samples under study, 4.14% of them were resistant to one or more drugs, and 5.77 and 3.04% had resistant genotypes in new and previously treated patients, respectively. Total resistance for each drug was 0.43% for dapsone, 3.19% for rifampicin and 1.17% for ofloxacin. We found statistically significant differences for rifampicin and for the total population when comparing the results from untreated versus previously treated patients. Two thirds of the resistant samples were resistant to rifampicin alone or combined. The standard multidrug therapy schemes continue being effective for leprosy cases; however, it is necessary to guarantee adherence and regularity. Surveillance to drug resistance in new and previously treated leprosy cases should be established.

Multifocal Osteoarticular Tuberculosis in Children

To review records of 16 children with multifocal osteoarticular tuberculosis. Records of 7 girls and 9 boys aged one to 14 (mean, 6) years with multifocal osteoarticular tuberculosis were reviewed. Haematological tests and radiographs of the chest, whole spine, pelvis, knees, elbows, hands, and feet were taken. The diagnosis was confirmed histologically. Patients were treated with standard 4-drug antitubercular chemotherapy (isoniazid, rifampicin, ethambutol, pyrazinamide) for 2 months, followed by a 2-drug regimen (isoniazid and rifampicin) for 10 months. Supportive treatment (deworming and nutritional advice) was also provided. All 16 patients were immunocompetent. Pain and swelling around the lesions were the main symptoms; fever was not common (2 cases only). No patient reported weight loss or night sweats. The mean number of bony lesions was 3.4 (range, 2-15) per patient. Appendicular (hands and feet) involvement was more common than axial (spinal) involvement. Radiological appearances of the lesions were cystic, irregular, lytic, and with or without sequestrum/ periosteal reaction. Some lesions were asymptomatic and detected incidentally on radiographs. Only one patient had active chest lesions. Five patients had spinal involvement but no neurological deficit. No patient underwent any surgical intervention, except for diagnostic biopsy. The mean follow-up period was 18 (range, 6-24) months. All patients showed complete healing within one year of chemotherapy. There were residual deformities and restriction of joint movement in patients with advanced articular and axial osteoarticular involvement. Children with multifocal osteoarticular tuberculosis were usually immunocompetent. Appendicular involvement was common, but concomitant chest involvement was uncommon. Standard multidrug antitubercular therapy and nutritional supplementation achieved good outcome.

Serum cytokine profile in leprosy and its correlation with clinico-histopathological profile

To analyse the serum levels of cytokines in leprosy patients, to correlate them with clinico-histopathological profile, and to study the effect of standard multidrug therapy on serum cytokine levels. Serum immunoassays of TNF-alpha, IFN-gamma, IL-1 beta and IL-10 were performed by ELISA in 61 newly diagnosed cases of leprosy before starting therapy and during reactional episodes. Of these, cytokine assays could be performed in 17 cases after completion of therapy. Levels of all the studied cytokines were significantly raised in cases compared to controls (P < 0.05). Levels of TNF-alpha and IFN-gamma were significantly raised in paucibacillary cases whereas all the studied cytokines were raised in multibacillary cases with rise in IL-1 beta and IL-10 being statistically significant (P < 0.001). No significant difference was however noted between TT and BT type; and BB, BL and LL types. All the studied cytokines were raised in reactional cases as compared to non-reactional cases. Comparing Type 2 reaction (T2R) and Type 1 reaction (T1R) cases, levels of IFN-gamma, IL-1 beta and IL-10 were higher in T2R cases but only IL-10 was found to be statistically significant (P = 0.05) while TNF-alpha was higher in T1R cases. Post therapy serum levels of all the studied cytokines were significantly lower than pretherapy levels (P < 0.05) and were comparable to controls. Among the paucibacillary cases, levels of all the cytokines were seen to decrease after 6 months of standard multidrug therapy. In the multibacillary cases, mean levels of the cytokines were found to decrease after 1 year of therapy except IFN-gamma. Serum cytokine estimation may have a significant role in classifying various forms of leprosy and can be used to monitor therapy.