Evaluation of New Antibacterial Drugs and their Combinations in a Murine Model to Identify Short Duration Alternative Chemotherapy for Leprosy.

The objective of the research is to test the efficacy of new drugs and drug combinations in mice infected with Mycobacterium leprae (M. leprae) as alternative to current WHO MDT. Individual drugs tested were Rifampicin (RMP), Rifapentine (RPT) and Moxifloxacin (MOXI). Drug combinations were RMP, Clarithromycin (CLARI), Minocycline (MINO) and RMP, MINO and Ofloxacin (OFLO). RPT drug combinations were RPT, CLARI, MINO and RPT, OFLO, MINO. Both the drugs and drug combinations were used as daily regimen and intermittent regimen. WHO MB MDT served as a positive control. Mice pre-inoculated with M. leprae were allotted to daily and intermittent groups and administered selected drugs and drug combinations. At the end of 12 months post sub-inoculation, mice were sacrificed and the proportion % of viable bacilli were counted using Spearman and Karber method. It was noted that RMP, RPT and Moxifloxacin indicated a range of 89.99% to 99.99% bactericidal effect when used in daily or intermittent doses in both normal and TR mice. Drug combinations showed bactericidal effect comparable to that of WHO MDT. From the study it was concluded that if the present duration of MDT has to be shortened then daily dose regimen with RMP/MINO/OFLO or RPT/CLARI/MINO are recommended for a clinical trial.

Evaluation of anti-bacterial activity of Rifapentine, Clarithromycin, Minocycline, Moxifloxacin, Ofloxacin and their combinations in Murine Model of Rifampicin Resistant Leprosy.

Leprosy, a debilitating disease of the skin and peripheral nerves is caused by Mycobacterium leprae (M. leprae) and is treated by multidrug therapy (MDT) comprising of Dapsone, Rifampicin and Clofazimine. Resistance to any of these drugs poses a threat to the current disease control strategies. With the emergence of Rifampicin resistance in leprosy, it is important that alternative drugs need to be tested to develop a treatment strategy to combat drug resistant leprosy. In the current study, we have investigated WHO MDT, Rifapentine, Clarithromycin, Minocycline, Moxifloxacin, Ofloxacin and their combinations in intermittent and daily dose regimens in rifampicin resistant strains of M. leprae through mouse foot pad experiments in order to determine the loss in viability of M. leprae in response to these drugs and their combinations. Our findings suggest that WHO MDT is still the best combination in Rifampicin resistance cases. Combination of Moxifloxacin with Minocycline and Clarithromycin may also be taken up for clinical trials in cases with Rifampicin resistant leprosy. Rifapentine and Moxifloxacin can be effective alternative drugs to replace Rifampicin where required either in daily dose shorter duration regimens or intermittent dose longer regimen to treat resistant strains.

Acquired Blaschkoid dermatitis.

Acquired Blaschkoid dermatitis characterised by unilateral relapsing inflammatory disease along the lines of Blaschko. A 40-year-old Indian male presented with unilateral erythematous, itchy grouped papules on the left side of the chest, abdomen, back and left arm of 15 days duration. The eruption stopped abruptly at the midline of the torso, completely sparing the right side of the body. The lesions were arranged in whorls and streaks corresponding to the lines of Blaschko. Skin biopsy showed hyperkeratosis and features suggestive of sub-acute spongiotic dermatitis with lymphocytic infiltrate around the blood vessels in the dermis. Patient was diagnosed as a case of Blaschkoid dermatitis. To the best of our knowledge, this is the first case of this condition being reported from India.

Ehlers Danlos syndrome in two siblings.

Two cases of Ehlers-Danlos syndrome affecting two real brothers are being reported. Both of them presented with features of atrophy and hyperextensibility of skin, hypermobility of joints and scarring at the sites of trauma. The elder brother also had kyphoscoliosis and hypogonadism with testicular failure.

Post-kala-azar dermal leishmaniasis in Nepal.

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL) manifests as a skin eruption after healing of visceral leishmaniasis (VL), either spontaneously or as a result of treatment. This study was undertaken to describe the demographic, clinical, and histopathologic features of PKDL in Nepal. METHODS: Demographic, clinical, microbiologic, and histopathologic features and response to treatment were studied in 22 patients with PKDL from April 1998 to March 2000. RESULTS: PKDL accounted for 0.13% of all new dermatologic cases. There were 13 (59.1%) males and nine (40.9%) females. A past history of kala-azar was present in all but one patient. A family history of kala-azar was noted in eight (36.4%) patients. All patients presented with multiple types of lesion, except for two in whom only macular lesions were seen. Oral lesions in the form of nodules and plaques were seen in four patients. Generalized lymphadenopathy was present in five patients. Slit skin smears revealed Leishman-Donovan bodies (LDBs) in nine (40.9%) patients. In macular lesions, there was a sparse infiltrate of plasma cells, lymphocytes, or histiocytes in the upper dermis. There was a dense chronic inflammatory infiltrate comprising plasma cells, lymphocytes, histiocytes, and epithelioid cells in the entire dermis from papules, plaques, or nodules. Giemsa staining of biopsy specimens revealed LDBs in seven (38.9%) patients only. Fine needle aspiration from epitrochlear lymph nodes in two patients demonstrated LDBs. All patients responded well to treatment with minimal side-effects. CONCLUSIONS: This study emphasizes the need to be aware of the possibility of cases of PKDL in endemic regions of leprosy, as the conditions may be difficult to distinguish clinically and histopathologically.

Cicatricial pemphigoid--a case report.

Cicatricial pemphigoid (CP) occurring in a 60-year-old male is described. He had involvement of conjunctival, nasal and oral mucosae, in addition to skin lesions. Diagnosis was confirmed by histopathology. He responded well to oral steroids and dapsone. However, vision in one eye was lost.

Health in Bihar -- an overview.

PIP: This article presents an overview of the health situation in Bihar for the last 50 years. Although demographic improvements have been noted in the past years, the incidence of various diseases remains high and socioeconomic status low in Bihar. Protein-energy malnutrition, nutritional anemia and blindness are common. Safe drinking water and sanitary facilities are still not available to a large number of people. Furthermore, a number of communicable diseases are prevalent in the country. This is exemplified in the Kala-azar or visceral leishmaniasis epidemic in 1992, which reported 75,523 cases and 1417 deaths. Kala-azar cases have started rising again since 1996, and it is estimated that there might be another epidemic in the first decade of the 21st century if the situation is allowed to continue. Other infectious diseases, which threaten the health situation in Bihar, are malaria, tuberculosis, leprosy, and HIV/AIDS. Moreover, population and decadal growth rate have more than doubled over the last 40 years. Maternal mortality remains very high, but survival chances of children have increased due to immunization and other programs. In general, it was demonstrated that the present health situation in Bihar is a matter of grave concern, and requires an urgent solution.^ieng

On structural aspects of peptidoglycan of bacterial cell wall with special attention on mycobacteria by computer modelling.

The cell wall components of mycobacteria are said to be vitally linked with their pathogenicity. Peptidoglycan, one of the major cell wall component in most of the bacteria are multilayered in gram positive bacteria and it is diverse in nature for the Gram positive strain rather than gram negative. The cell wall of bacteria are primary targets for many drugs and antibiotics and conformation of the major cell wall components provide invaluable information and understanding at molecular level to medicinal chemists and drug designers. Mycobacterial peptidoglycan has been studied critically by computer modelling on various aspects. A plausible structure and conformation has been identified and glycan chain is found to have a pseudo two fold symmetry taking disaccharide unit as monomer with Knox & Murthy H-bond scheme. This paper attempts to clarify the understanding of organisation and possible interaction mode of peptidoglycan of organisation in complex mycobacterial cell wall structure.