Drug resistance in leprosy: An update following 70years of chemotherapy.

Leprosy is one of the oldest infectious diseases, reported for more than 2000years. Leprosy elimination goal as a public health problem set by the World Health Organization, aiming for a global prevalence rate<1 patient in a population of 10,000, was achieved in 2000 mainly thanks to the worldwide use of leprosy drugs starting in the 1980s and their access at no cost for patients since 1995. However, around 200,000 new cases are still reported each year, particularly in India, Brazil, and Indonesia. As with other bacteria of medical interest, antimicrobial resistance is observed in Mycobacterium leprae strains in several parts of the world, despite multidrug therapy being the recommended standard leprosy treatment to avoid resistance selection since 1982. Therefore, identifying and monitoring resistance is necessary. We provide an overview of the historical facts that led to the current drug resistance situation, the antibiotics effective against M. leprae, their mechanisms of action and resistance, and resistance detection methods. We also discuss therapeutic management of the resistant cases, new genes with potential roles in drug resistance and bacterial adaptation, new drugs under investigation, and the risk for resistance selection with the chemoprophylaxis measures.

Drug resistance in leprosy: an update following 70 years of chemotherapy

Leprosy is one of the oldest infectious diseases, reported for more than 2000 years. Leprosy elimination goal as a public health problem set by the World Health Organization, aiming for a global prevalence rate < 1 patient in a population of 10,000, was achieved in 2000 mainly thanks to the worldwide use of leprosy drugs starting in the 1980s and their access at no cost for patients since 1995. However, around 200,000 new cases are still reported each year, particularly in India, Brazil, and Indonesia. As with other bacteria of medical interest, antimicrobial resistance is observed in Mycobacterium leprae strains in several parts of the world, despite multidrug therapy being the recommended standard leprosy treatment to avoid resistance selection since 1982. Therefore, identifying and monitoring resistance is necessary. We provide an overview of the historical facts that led to the current drug resistance situation, the antibiotics effective against M. leprae, their mechanisms of action and resistance, and resistance detection methods. We also discuss therapeutic management of the resistant cases, new genes with potential roles in drug resistance and bacterial adaptation, new drugs under investigation, and the risk for resistance selection with the chemoprophylaxis measures.

Genome-wide re-sequencing of multidrug-resistant Mycobacterium leprae Airaku-3.

Genotyping and molecular characterization of drug resistance mechanisms in Mycobacterium leprae enables disease transmission and drug resistance trends to be monitored. In the present study, we performed genome-wide analysis of Airaku-3, a multidrug-resistant strain with an unknown mechanism of resistance to rifampicin. We identified 12 unique non-synonymous single-nucleotide polymorphisms (SNPs) including two in the transporter-encoding ctpC and ctpI genes. In addition, two SNPs were found that improve the resolution of SNP-based genotyping, particularly for Venezuelan and South East Asian strains of M. leprae.

[Health-related quality of life in patients with chronic kidney disease]. / Qualita' della vita nei nefropatici.

Assessment of quality of life in patients with different degrees of chronic kidney disease is an important issue because of its impact on clinical decisions and financial resource management in the health-care system. The aim of this study was to assess whether a generic instrument like the SF-36 questionnaire is able to discriminate three different populations of patients with different degrees of renal disease (pre-ESRD, ESRD, TxR). Five hundred sixty-three patients from 12 Italian nephrology units completed the SF-36 scales by themselves. The results from these samples were compared with those from the general population. Univariate analysis and multivariate regression were used. The generic SF-36 questionnaire proved to be a powerful instrument to discriminate populations with different degrees of chronic renal failure. The quality of life of patients on dialysis is significantly worse than that of the normal population and other patients with less severe renal function impairment.

[Acute biocompatibility of hemodiafiltration with endogenous reinfusion (HFR)]. / Emodiafiltrazione con reinfusione endogena (HFR): profilo di biocompatibilità in acuto.

PURPOSE: In order to reduce the hemodialysis (HD)-induced pro-inflammatory activity we need to use a biocompatible dialysis membrane, avoid backfiltration and possibly use adsorbents. Hemodiafiltration reinfusion (HFR) is a new on-line hemodiafiltration (HDF) technique combining these aspects. This study aimed to evaluate the biocompatibility of the single dialysis session comparing standard HD and HFR. METHODS: Eighteen patients on chronic HD were enrolled in five Centers. Patients underwent one standard and two HFR study sessions; in each session we evaluated leukocyte activation at 0, 5, 15, 60 and 240 min; and interleukin-6 (IL-6), C-reactive protein (CRP) and IL-1 receptor antagonist (IL-1Ra) levels at 0, 60 and 240 min. RESULTS: Leukocyte activation was similar in HD and HFR, while the post-dialysis IL-6 increase was lower with HFR; CRP levels were stable during HFR, but increased after HD, and IL-1Ra did not demonstrate any difference. CONCLUSIONS: These preliminary data show that HFR still has a better biocompatibility in the single dialysis session.

[A case of IgM-secreting myeloma]. / Un caso di mieloma IgM secernente.

The authors describe a case of multiple myeloma, with the typical aspects of bone marrow and with bone lesion, in presence of monoclonal IgM secretion. Polychemotherapy proved effective transitorily. The clinical period had, as complication, the occurrence of breast cancer. The terminal period was characterized by irreversible renal failure.

Improvement of continuous arteriovenous hemofiltration (CAVH) and hemofiltration (HF) efficiency by adding hemoperfusion (HP).

Aiming to improve the efficiency of the blood purification convective methods either with spontaneous (CAVH) or with pump-assisted (HF) extracorporeal circulation we inserted after the hemofilter a cartridge containing 70 g of collodion-coated activated charcoal (CAC) microencapsulated, obtaining so hemofiltration and hemoperfusion in series (HF+HP). The obtained results show that in both methods HP addition gives a negligible increase of urea clearance and a practically null increase of phosphate clearance, whereas creatinine and uric acid clearances increase is remarkable especially, in percentage, with low blood flows (CAVH). In the HF+HP system we have also been studying B2-microglobulin (B2-M) clearance aiming at examining the possibility of increasing the removal of substances with higher molecular weight. We have been finding HP addition increases further on B2-M clearance already high in HF. Therefore we think HP addition to convective methods is an interesting step in the attempt to carry out highly efficient blood purification methods.

[Hemofiltration and hemoperfusion performed in series for the purpose of removing beta 2 microglobulin]. / Hemofiltrace, hemoperfúze provádená v sériích za úcelem odstranování beta 2-mikroglobulinu.

With the objective to develop most efficient method for Beta-2-microglobulin elimination, the authors, using extracorporeal circulation placed behind the haemofilter a capsule containing 70 g of collodion coated with activated medicinal charcoal. This combination was used in 3 haemofilters made from different membranes. The results showed polysulphon to be the highest efficiency membrane out of those tested for Beta-2 microglobulin elimination. In combination with haemoperfusion, its efficiency increases significantly. Even if haemoperfusion increases efficiency by considerable percentage, the Beta-2 microglobulin elimination using other types of membranes lasts long and the total clearance remains low.

[Sclerodermic heart. Report of a case with malignant evolution (author's transl)]. / Il cuore sclerodermico. A proposito di un caso ad evoluzione maligna.

In progressive systemic sclerosis, cardiac involvement, evidenced by histology, is rather unusual and even more rarely it gives clinical manifestations. In our patient cardiac symptoms, characterized by recurrent pulmonary edema as well as by serious conduction defects and arrhythmias, are prevailing and have a rapid and fatal course, whereas the involvement of the skin and of other internal organs is not important. The post-mortem examination gives an evident explanation of the clinical course of the disease, which we can consider as a typical manifestation of sclerodermic heart.