Treatment Of Leprosy Research Articles

Dioscorea bulbifera, a highly threatened African medicinal plant, a review

Dioscorea bulbifera bulbils are used in the treatment of Piles, dysentery, syphilis, ulcers, cough, leprosy, diabetes, asthma, and cancer. It is a raw material for contraceptives, and it is one of ...

From Turkey with Love: Deycke's Nastin Treatment of Leprosy in Queensland, 1909 to 1913

From Turkey with Love: Deycke's Nastin Treatment of Leprosy in Queensland, 1909 to 1913

From Turkey with Love: Deycke's Nastin Treatment of Leprosy in Queensland, 1909 to 1913

In the early part of the twentieth century, there was no proven treatment for leprosy. In 1904 Georg Deycke, a German physician working in Constantinople, announced that he had discovered an apparently successful treatment. He recognised that the drug (‘nastin’) was potentially dangerous and should be used only when patients could be closely monitored. This paper explores how Deycke came to believe that his treatment worked, and how it came to be used in Queensland, where the leprosarium established in 1907 was in a state of disorder as tensions between medical authorities, politicians, staff, and patients escalated. It was an inappropriate place for a trial of nastin. By 1913, nastin had shown no significant effects and its use was discontinued in Queensland and around the world.

A rare case report on dapsone induced haemolytic anaemia in a hansen’s disease patient with type-1 leprae reactions

Dapsone also known as diaminodiphenyl sulfone is a principal drug in a multidrug regimen recommended by the WHO used for the treatment of leprosy. It is a potent anti-inflammatory and anti-parasitic compound mainly used in the treatment of wide variety of dermatological inflammatory diseases. A 58 years old male patient was admitted in the dermatology ward with chief complaints of body pains, scaly red raised lesions all over the body since 10 days. His past medical history includes h/o BB (Borderline Borderline) leprosy & started MB–MDT (is a combination of Tab. Dapsone, Tab. Rifampicin, Tab. Clofazimine) since 2 months. Now he developed ­ erythema & scaling of lesions in body & body pains, burning sensation of eyes since 10 days. Dapsone is associated with seven fold increased risk of hemolytic anemia so better vigilance is necessary for implementation of safe and effective treatment for each individual.

DDS promotes longevity through a microbiome-mediated starvation signal

The antibiotic diaminodiphenyl sulfone (DDS) is used in combination with other antibiotics as a first line treatment for leprosy. DDS has been previously reported to extend lifespan in Caenorhabditis elegans through inhibition of pyruvate kinase and decreased mitochondrial function. Here we report an alternative mechanism of action by which DDS promotes longevity in C. elegans by reducing folate production by the microbiome. This results in altered methionine cycle metabolite levels mimicking the effects of metformin and lifespan extension that is dependent on the starvation- and hypoxia-induced flavin containing monoxygenase, FMO-2.

Factors Contributing to Delay in Diagnosis and Start of Treatment of Leprosy: Analysis of Help-seeking Narratives from a Community Study in Dang District

Prolonged delays between first symptoms and diagnosis easily result in more impairment in newly detected leprosy patients, and aggregate negative consequences for individuals and their families. In cases of infectious leprosy, longer delays increase the risk for the spread of the disease. Limited studies have been carried out to explore the causes for delays in Nepal. This is a community level qualitative study conducted in Dang district. The information was obtained through in-depth interviews with 8 leprosy affected persons, 8 contacts, 8 community members and 5 service providers in Dang district. Skin patches were regarded as a simple skin disease, in particular of paucibacillary patients who had a limited number of skin lesions and no nerve damage. A local medical shop was the first choice for medicine to treat skin conditions. Delays in diagnosis of leprosy occurred at many stages from the development of the symptoms to consultation of health care services. The use of traditional medicine, a belief in self-cure and visit to traditional healers, and misdiagnosis (a disease other than leprosy by the health worker) and inadequate knowledge about the disease and its early symptoms were the main factors that influenced the delayed diagnosis. Delays accumulated as the result of series of help-seeking actions that reflected local socio-cultural beliefs and practices. Misdiagnoses could be reduced if adequate information on leprosy is given to community people and health service providers. Specific interventions are needed to promote knowledge and a good attitude among contacts and community members. To reduce patient delay, public health promotion is needed to increase the awareness of leprosy, and the health service delay should be reduced by improving diagnostic skills in public and private sectors. Addressing both components of delays will decrease the time to diagnosis and ultimately the extent of transmission of the disease and reduce the risk of nerve function impairments.

Poor treatment compliance leads to a higher mutation for rifampicin resistance in multibacillary leprosy patients

Background: Multidrug therapy (MDT) is a safe and effective drug combination for leprosy treatment that can prevent drug resistance. Mycobacterium leprae resistance, especially to rifampicin, is a serious problem as it potentially thwarts the worldwide leprosy-elimination program by the World Health Organization (WHO). One of the suspected causes of rifampicin resistance is poor treatment compliance. It was necessary to assess the association between the treatment compliance and the occurrence of mutation rifampicin resistance in multibacillary (MB) leprosy patients.Methods: A comparative, analytical, cross-sectional study was performed in MB leprosy patients who had completed treatment at the Dermatovenereology Outpatient Clinic in Cipto Mangunkusumo Hospital and the Sitanala Center for Leprosy Hospital from Oc­tober 2012 to April 2013. Based on treatment regularity and history of drug discontinuation, the subjects were classified as either having good or poor compliance. Skin smear from a slit skin smear (SSS) examination was further analyzed by using the polymerase chain reaction (PCR) sequencing technique to detect rifampicin resistance.Results: Fifty-seven study subjects were enrolled in this study. In the good treatment compliance group (29 subjects), only 1 case of mutation for rifampicin resistance was found. Meanwhile, in the poor drug compliance group (28 subjects), 8 cases of mutation for resistance (29%) were found. This difference in mutation rate was statistically significant (OR=11.2; 95% CI=1.296–96.787; p=0.012).Conclusion: This study revealed that the risk of occurrence of M. leprae resistance to rifampicin in patients with poor drug compliance was significantly higher than in those with good drug compliance.

A Prospective Review on Phyto-Pharmacological Aspects of Andrographis paniculata

Andrographis paniculata Nees is an annual herbaceous plant which belongs to the family Acanthaceae. It is commonly known as Kalmegh, is found in the plains of India, China, Pakistan, Sri Lanka and South Asia and is native to India and Sri Lanka. Kalmegh is known to be the “king of bitters” though it is of small size and it also has a similar appearance and taste as that of the Neem plant. It is one of the widely used effective medicinal plants in the world. All parts of this plant are used to extract the potential phytochemical, but the composition of phytoconstituents mostly differs from one part to another in a season, place and time of harvest. It is a traditional medicinal plant widely used in the treatment of anti-inflammatory, anti-bacterial, anti-oxidant, hepatoprotective, hematocidal, anti-HIV, anti-cancer, anti-diabetic, arthritis, rheumatism, cough, cold, multiple sclerosis, depression, diarrhoea, dysentery, candida, fevers, herpes, leprosy, malaria, jaundice, tuberculosis and several infectious diseases ranging from malaria to dysentery. The plant is widely used in Ayurvedic and homeopathic system of medicine. The medicinal value of this plant is due to the active ingredients via andrographolide and neoandrographolide, which are derivative of diterpinoids. It prevents oxidative damage and inhibits binding of toxic metabolite to DNA.

Insights on Mycobacterium leprae Efflux Pumps and Their Implications in Drug Resistance and Virulence.

Drug resistance in Mycobacterium leprae is assumed to be due to genetic alterations in the drug targets and reduced cell wall permeability. However, as observed in Mycobacterium tuberculosis, drug resistance may also result from the overactivity of efflux systems, which is mostly unexplored. In this perspective, we discuss known efflux pumps involved in M. tuberculosis drug resistance and virulence and investigate similar regions in the genome of M. leprae. In silico analysis reveals that the major M. tuberculosis efflux pumps known to be associated with drug resistance and virulence have been retained during the reductive evolutionary process that M. leprae underwent, e.g., RND superfamily, the ABC transporter BacA, and the MFS P55. However, some are absent (DinF, MATE) while others are derepressed (Mmr, SMR) in M. leprae reflecting the specific environment where M. leprae may live. The occurrence of several multidrug resistance efflux transporters shared between M. leprae and M. tuberculosis reveals potential implications in drug resistance and virulence. The conservation of the described efflux systems in M. leprae upon genome reduction indicates that these systems are potentially required for its intracellular survival and lifestyle. They potentially are involved in M. leprae drug resistance, which could hamper leprosy treatment success. Studying M. leprae efflux pumps as new drug targets is useful for future leprosy therapeutics, enhancing the global efforts to eradicate endemic leprosy, and prevent the emergence of drug resistance in afflicted countries.

Recent Advancement in the Diagnosis and Treatment of Leprosy.

Many of the tropical diseases are neglected by the researchers and medicinal companies due to lack of profit and other interests. The Drugs for Neglected Diseases initiative (DNDi) is established to overcome the problems associated with these neglected diseases. According to a report published by the WHO, leprosy (Hansen's disease) is also a neglected infectious disease. A negligible amount of advancements has been made in last few decades which includes the tools of diagnosis, causes, treatment, and genetic studies of the bacterium (Mycobacterium leprae) that causes leprosy. The diagnosis of leprosy at earlier stages is important for its effective treatment. Recent studies on vitamin D and its receptors make leprosy diagnosis easier at earlier stages. Skin biopsies and qPCR are the other tools to identify the disease at its initial stages. Until now a specific drug for the treatment of leprosy is not available, therefore, Multi-Drug Therapy (MDT) is used, which is hazardous to health. Besides Mycobacterium leprae, recently a new bacterium Mycobacterium lepromatosis was also identified as a cause of leprosy. During the last few years the genetic studies of Mycobacterium leprae, the role of vitamin D and vitamin D receptors (VDR), and the skin biopsies made the treatment and diagnosis of leprosy easier at early stages. The studies of micro RNAs (miRNAs) made it easy to differentiate leprosy from other diseases especially from tuberculosis. Leprosy can be distinguished from sarcoidosis by quantitative study of reticulin fibers present in skin. The treatment used until now for leprosy is multi-drug treatment. The complete genome identification of Mycobacterium leprae makes the research easy to develop target specified drugs for leprosy. Rifampicin, identified as a potent drug, along with other drugs in uniform multi-drug treatment, has a significant effect when given to leprosy patients at initial stages. These are effective treatments but a specific drug for leprosy is still needed to be identified. The current review highlights the use of modern methods for the identification of leprosy at its earlier stages and the effective use of drugs alone as well as in combination.

Severe adverse reactions to multidrug therapy for leprosy, registered in tertiary services between 2012 and 2017 in Brazil

Objectives: This work aims to determinate the main severe adverse reactions to multidrug therapy (MDT), as well as the characteristics of the patients who had them and the period when they were more prevalent. Results: Of the 158 patients undergoing treatment for leprosy in the period 2012–2017, 22 (13.9%) were using substitutive treatment for leprosy and presented criteria to enter this study. Adverse reactions were more frequent in women (59.1%), above 45 years age and during second month of treatment. Dapsone was the most frequently implied drug (86.4%), and hemolytic anemia was the main reaction (72.7%). Conclusion: Severe adverse reaction to dapsone is common in MDT, mainly due to hemolytic anemia.

Leprosy: Cause, Symptons and Treatment.

Leprosy is considerd to be a very severe degenerative and communicable disease since long. This disease is caused by bacillus Mycobacterium leprae or Mycobacterium leprometosis or Mycobacterium leprimurium, which is expressed as nodes on the body or degeneration of body parts especially of hand and legs. There is a detailed description of symptoms and treatment of leprosy in ancient Ayurvedic medical litrature. In morden medical system multi drug therapy treatment is used, combining Rifampcin, Ofloxcin and Minocycline antibiotics which are very effective. Inspite of that in Indian sub continent very effective results were not found due to lack of awareness and education, although improvement is visible now.

Synthesis and Characterization of a Biomimetic Formulation of Clofazimine Hydrochloride Microcrystals for Parenteral Administration.

Clofazimine (CFZ) is a broad spectrum antimycobacterial agent recommended by the World Health Organization as a first line treatment for leprosy and second line treatment for multidrug resistant tuberculosis. Oral administration of CFZ leads to a red skin pigmentation side effect. Since CFZ is a weakly basic, red phenazine dye, the skin pigmentation side effect results from lipophilic partitioning of the circulating, free base (neutral) form of CFZ into the skin. Here, we developed a stable and biocompatible formulation of CFZ-HCl microcrystals that mimics the predominant form of the drug that bioaccumulates in macrophages, following long term oral CFZ administration. In mice, intravenous injection of these biomimetic CFZ-HCl microcrystals led to visible drug accumulation in macrophages of the reticuloendothelial system with minimal skin accumulation or pigmentation. In fact, no skin pigmentation was observed when the total amount of CFZ-HCl administered was equivalent to the total oral dose leading to maximal skin pigmentation. Thus, parenteral (injected or inhaled) biomimetic formulations of CFZ-HCl could be instrumental to avoid the pigmentation side effect of oral CFZ therapy.

Worsening of the disability grade during leprosy treatment: prevalence and its determinants in Southern Nigeria.

In Nigeria, little is known about the development of new or additional physical disability during leprosy treatment. The objective of this study was to determine the prevalence and evaluate factors associated with worsening of physical disability during leprosy treatment in Nigeria. This was a retrospective cohort study conducted among leprosy patients treated in six referral facilities in six States in Nigeria between January 2011 and December 2015. Multivariable logistic regression analysis was used to identify predictors of worsening disability after treatment. Of 984 leprosy patients who completed treatment, the mean age of the patients was 39.8±17.6 years and 57.4% (565/984) of them were male. Also, 51.6% (508/984) of the patients had either grade 1 or 2 disability at diagnosis, but this declined to 30.8% (303/984) following treatment (p<0.001). Overall, 4.7% (46/984) of the cases developed new or additional disability (or worsening disability) during treatment. The cases with the greatest odds for developing worsening physical disability were patients from the southwest (adjusted odds ratio [aOR] 15.9; 95% CI 3.8-67.4) and southeast zones (aOR 4.7; 95% CI 1.1-19.2), and patients who had a leprosy reaction requiring additional corticosteroid therapy (aOR 11.7; 95% CI 4.4-31.2). Sustained capacity building for health professionals on better monitoring and management of leprosy and its complications is strongly recommended in Nigeria.

New therapeutic patents used for the treatment of leprosy: a review.

Leprosy is a granulomatous disease, infectious and transmissible, which affects the skin and peripheral nerves, having Mycobacterium leprae as causative agent. The manifestation of this disease causes cutaneous lesions, peripheral neuropathies and, in more extreme cases, may generate deformities and disabilities in affected individuals. Patents were identified using the descriptor 'leprosy' and code A61K of the international patent classification, which indicates only products that meet human needs. The analysis was made using the WIPO, ESPACENET and USPTO databases, until the month of September 2016. Through this review, we found a variety of in vitro, pre-clinical and clinical studies relating to the treatment of leprosy with different types of compounds and forms of administration. New treatment proposals should include pain reduction capabilities, prevention or limitation of the appearance of cutaneous lesions, as well as prevention of the progression of the disease to more severe stages that may lead to loss of function or potentiate the individual's immune response to the M. leprae bacillus in order to prevent bacterial spread. We concluded that any patents developed with natural products were not found in the treatment of leprosy. All the deposited products were synthetic origin, mostly tested in humans and of varied forms of administration.

Chromatographic method for the simultaneous quantification of dapsone and clofazimine in nanoformulations.

The low bioavailability and nonspecific distribution of dapsone and clofazimine, commonly applied in combination for the treatment of leprosy, can produce toxic effects. Nanotechnological approaches enhance the delivery of these drugs. Therefore, a high-performance liquid chromatography method was developed for the simultaneous determination of dapsone and clofazimine loaded in nanoformulations for quality control purposes. Chromatographic separation was achieved on a reversed-phase Kinetex core-shell C18 column, followed by spectrophotometric detection at 280nm. Considering the different physicochemical properties of dapsone and clofazimine, elution was performed in gradient mode using an aqueous acetate buffer (50mmol/L, pH 4.8) and an increasing acetonitrile content from 27 to 63% v/v at a flow rate of 1.0mL/min with retention times of 6.2 and 14.0min, respectively. The method was validated according to the European Medicines Agency guideline and it was found to be specific, accurate (99.6-114.0%), and precise for intra- (RSD≤1.8%) and interday assays (RSD≤12.5%). Both drugs showed stability after 24h at room temperature and over three freeze-thaw cycles with recoveries ≥86.2%. Low temperature (4°C) in the autosampler caused the precipitation of clofazimine and must be avoided. The validated method was successfully applied in the quantification of both drugs in nanoformulations.

Medicinal properties of Abutilon indicum

Abutilon indicum is a common Indian shrub, belonging to the family Malvaceae; Also known as Mallow in english, Abutilon indicum is used as a medicinal plant. It has been extensively used as a traditional medicine as a laxative, emollient, analgesic, anti-diabetic, anti-inflammatory and blood tonic agent and also in the treatment of leprosy, urinary disease, jaundice, piles, relieving thirst, cleaning wounds and ulcers, vaginal infections, diarrhea, rheumatism, mumps, pulmonary tuberculosis, bronchitis, allergy, blood dysentery, some nervous and some ear problems. Various studies on the plant extract have been performed to confirm the anti-oxidant, anti-bacterial, analgesic, anti-inflammatory, anti-cancer, hepato-protective, immuno-modulatory and larvicidal activities of the plant. This plant is often used as a medicinal plant and is considered invasive on certain tropical islands. In traditional medicine, A. indicum is used as a aphrodisiac, demulcent, diuretic, laxative, pulmonary and sedative (leaves). The bark is astringent and diuretic; laxative, expectorant and demulcent (seeds); laxative and tonic, anti-inflammatory and anthelmintic (plant); analgesic (fixed oil); diuretic and for leprosy (roots). The plant is very much used in Siddha medicines. In fact, the bark, root, leaves, flowers and seeds are all used for medicinal purposes by Tamils. The leaves are also used to treat for pile complaints. The flowers are traditionally used to increase semen in men. The phytochemical analysis showed the Presence of Alkaloid, Saponins, Amino acid, Flavonoids, Glycosides and steroids. This plant exhibits several potential pharmacological activities. A review on the various studies on the plant has been provided for the purpose of understanding its medicinal properties.

Medicinal properties of Abutilon Indicum

Abutilon indicum is a common Indian shrub, belonging to the family Malvaceae; Also known as Mallow in english, Abutilon indicum is used as a medicinal plant. It has been extensively used as a traditional medicine as a laxative, emollient, analgesic, anti-diabetic, anti-inflammatory and blood tonic agent and also in the treatment of leprosy, urinary disease, jaundice, piles, relieving thirst, cleaning wounds and ulcers, vaginal infections, diarrhea, rheumatism, mumps, pulmonary tuberculosis, bronchitis, allergy, blood dysentery, some nervous and some ear problems.

Antimicrobial activity of ipolamiide isolated from the stembark of &lt;i&gt;Stereospermum kunthianum&lt;/i&gt; Cham (Bignoniaceae)

Stereospermum kunthianum (Bignoniaceae) plant is used in traditional ethnomedicine in treating bronchitis, venereal diseases, diarrhoea and dysentery. It is also used in the treatment of ulcers, leprosy, skin eruptions, respiratory ailments and gastritis. In continuation of our study of the activity of Stereospermum kunthianum , we subjected the compound ipolamiide, previously isolated and characterized, to antimicrobial study. The antimicrobial activity of ipolamiide was studied using agar cup plate and broth dilution methods against the following clinical isolates; Escherichia coli , Staphylococcus aureus , Methicillin resistant Staphylococcus aureus , Shigella dysenteriae , Klebsiella pneumoniae , Candida albicans , Candida krusei , Candida tropicalis and Pseudomonas aeruginosa . The results of antimicrobial screening showed that all the organisms tested were susceptible to ipolamiide and was found to be active against Staphylococcus aureus , Streptococcus pneumoniae , Klebsiella pneumoniae , Escherichia coli , Salmonella typhi for the bacteria and Candida krusei for the fungi. It was found to be inactive against Methicillin resistant Staphylococcus aureus (MRSA), Shigella dysenteriae and Candida albicans and Candida tropicalis . The compound showed zone of inhibition ranging from 21–29mm against all the tested microorganisms except MRSA and Shigella dysenteriae , standard antibiotic drugs erythromycin and fluconazole at concentrations of 5μg/ml each showed zones of inhibition ranging from 32 – 41mm for erythromycin except the Candidas while Fluconazole showed zones of inhibition ranging from 32 – 35mm for the Candidas . Keywords: Stereospermum kunthianum ; Antibacterial activity; Paper disc diffusion; Phytochemical screening

Tuberculosis and Leprosy Coinfection: A Perspective on Diagnosis and Treatment

Both leprosy and tuberculosis (TB) are known to have similar geographic endemicity. In the setting of coinfection, interferon-gamma release assays (IGRAs) to detect latent TB can be falsely positive. We report a case of leprosy with a positive IGRA and asymptomatic active pulmonary TB. Minocycline and dapsone therapy was initiated during the workup for TB and changed to rifampin (Rif), isoniazid, pyrazinamide, and ethambutol, with the addition of dapsone once coinfection was confirmed. Our review of the literature revealed a preponderance of coinfection reported with borderline and lepromatous disease. Ten patients were diagnosed with leprosy as the first infection; 7 of these patients (70%) were treated with Rif before TB diagnosis, and 70% (7/10) of coinfected patients were on steroids. If treatment for leprosy is a consideration before ruling out active TB, then minocycline may temporarily replace the Rif. The dire implications of Rif monotherapy in undiagnosed coinfection may warrant chest radiography with or without sputum microbiology as routine initial workup for all leprosy cases.