Mycobacterium leprae in India

Contents

   * 1 Introduction
           1.1 Classification
           1.2 General
           1.3 History
   * 2 Description of Mycobacterium leprae
           2.1 Genome
           2.2 Transmission
           2.3 Symptoms
           2.4 Prevention
           2.5 Treatment
   * 3 Why is this disease a problem in India
   * 4 Leprosy in Present Day
   * 5 External Links
   * 5 References

Introduction

1.1 Classification
Bacteria Actinobacteria Actinobacteridae Actinomycetales Corynebacterineae Mycobacteriaceae Mycobacterium leprae

1.2 General
Mycobacterium leprae causes the chronic infectious disease called leprosy also known as Hansen's disease named after Gerhard Henrik Armauer Hansen (29 July 1841 – 12 February 1912) a Norwegian physician, who was the first to identify it in 1873 as the causative agent of leprosy. (2) M. leprae is a gram-positive rod-shaped, acid-fast bacillus. The disease mainly affects the skin, the peripheral nerves, mucosa of the upper respiratory tract and also the eyes, apart from some other structures. (3)

1.3 History
Leprosy in India dates as far back as the second millennium B.C. Recent findings of a male skeleton, after being tested for age, shows that the skeleton is from 2000 B.C. The skeleton shows symptoms of leprosy including degenerative joint disease and injury to the peripheral skeleton. This skeleton is the oldest evidence of leprosy in India. (Robbins)

Olden India categorized two types of leprosy: anaesthetic and tuberculated. Lepra anaesthetica is a more rare form of the two. It alters cutaneous nerves of body parts. Lepra tuberculosa is the general form of leprosy. It deteriorates the skin and tissues of the body. (7) Symptoms described from olden India perfectly match what are the current symptoms of Kushtha (leprosy in Indian) today. The disease has been known to exist in India for, at the very minimum, three thousand years. (11) About twenty persons out of ten thousand had this disease. (7) Some cases of leprosy have extremities in terms of duration, how long the disease affects the patient. The shortest duration in a case has been one year, and the longest duration has been up to forty years. (54)

Leprosy seemed to be especially prevalent in the district of Kumaun in the late 1800’s. (23) In a statistical study, the disease was more prominent in the eastern side of the district rather than the western side. (26) Research showed that there would not be an increase in leprosy of the population of Kumaun, as long as the disease was hereditary. (71)

In a 1852 census, for every four males that had leprosy, only one female had leprosy. In the previous census, the ratio for males to females with leprosy was almost ten to one. For some reason, the leprosy ratio decreased rapidly. (25) However, with more recent studies, it seems that leprosy has been affecting females more than males (53). For ages 20-30, the percentage of males diseased is 20.0% whereas for females the percentage is 26.4% (53).

Description of Mycobacterium leprae

2.1 Genome
The complete sequence is 3,268,203 bp in length with a G+C content of 57.8%, and was generated from a combination of cosmid and 6-fold whole-genome shotgun sequencing. The start of the sequence is the first base of the dnaA gene, close to the origin of replication. There are 1,604 protein-coding genes and 1,116 pseudogenes. Both the sequence and annotation have been deposited in the public databases (NCBI) with the accession number AL450380.http://www.ncbi.nlm.nih.gov/nuccore/30407142 The Sanger Institute sequenced Mycobacterium leprae in collaboration with the laboratory of Stewart Cole at the Unit de Genetique Moleculaire Bacterienne, Institut Pasteu. Sequencing was funded by the Heiser Program for Research in Leprosy and Tuberculosis of The New York Community Trust, L'Association Raoul Follereau, The Wellcome Trust, ILEP, and the Institut Pasteur.

2.2 Transmission of disease
Traditionally, mycobacterium leprae was known to infect and affect the skin, mainly through lining containing epithelial cells and also the peripheral nerves such as those contained in the central nervous system. However, recent research attempts to elaborate further into such findings to narrow down a specific mechanism of infection, which to this day, is still unknown. Although a specific method proves lacking, there seems to be various hypotheses surrounding this greatly debatable topic. Thus far, it has been postulated that mycobacterium leprae may gain access to entry through two primary routes- the nasal mucosal membrane or through skin injuries. However, it has been shown that passage through the nasal mucosal membrane may be the primary route of infection. A study, focusing primarily on the mce1A gene in mce1 operon (mammalian cell entry) of mycobacterium tuberculosis which proved to have a similar set of encoded proteins as mycobacterium leprae; experiment was to be done in vitro, to observe the cell uptake activity of polystyrene latex beads which are layered with purified recombinant r proteins expressed by a specific locus within the mce1A gene. The results showed that the r-protein did promote uptake of the polystyrene latex beads into human nasal mucosal cells which concludes that the mce1A gene could mediate the entry of mycobacterium leprae into respiratory mucosal tracts and may possibly be the main mode of transmission of such microbe. Additionally, endothelial cells may perhaps serve as a microbial reservoir, the cause of long-term infections. Unlike many other mycobacteriums, mycobacterium leprae does not only survive in macrophages in vivo, it can also survive in nonmacrophage cells such as epithelial cells (as shown previously) and Schwann cells. Extensive research has revealed that destruction of such nonmacrophage cells is the primary manifestation of the disease, leprosy. It has been found that a mycobacterium leprae gene encoding fibronectin (FN) binding protein is the main mechanism of transmission via epithelial and Schwann cells. The interaction between FAP-L (FN attachment protein) and FN is an important step in the pathogenesis of leprosy; FN acts as an oposinin.

2.3 Symptoms 2.4 Prevention 2.5 Treatment

Why is this disease a problem in India?

How is it transmitted? Is there a vector (animal/insect)? Prevention

Do lifestyle/environment/economics/political issues play a role? What is being done to address this problem

Include anything being done by the local government or groups as well as efforts by non-local groups. What else could be done to address this problem

Are there solutions that could be successful but haven't been implemented due to political or economic reasons? Are there successful efforts in other countries? Are there reasons why these efforts may or may not be successful in the country you've focused on? etc. etc. References

[Sample reference] Takai, K., Sugai, A., Itoh, T., and Horikoshi, K. "Palaeococcus ferrophilus gen. nov., sp. nov., a barophilic, hyperthermophilic archaeon from a deep-sea hydrothermal vent chimney". International Journal of Systematic and Evolutionary Microbiology. 2000. Volume 50. p. 489-500.

Edited by [Katherine Tang, Victor Tran, Natalie Nguyen, Julia Chu, Millie (Mei) Liu, Jason Wang], students of Rachel Larsen