Mycobacterium leprae -- Leprosy

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Pathogenic Microbiology in Italy [1]
"Mycobacterium leprae" globi in patient. From: Escholarship.org [2]
Woman with leprosy. From: Leprosymission.org [3]

Etiology/Bacteriology

Taxonomy

| Domain = Bacteria | Phylum = Actinobacteria | Class = Actinobacteridae | Order = Actinomycetales | Suborder = Corynebacterineae | Family = Mycobacteriaceae | Genus = Mycobacterium | Species = M. leprae |

NCBI: Taxonomy Genome: Mycobacterium leprae

Description

Pathogenesis

Transmission

Although much about the transmission of Mycobacterium leprae is unknown, prolonged contact with an infected person increases an individual's chance of becoming infected. Armadillos can harbor the bacteria, but are not seen as a threat to human contraction of the disease. In addition, insects could be possible carriers of Mycobacterium leprae but this is unclear In humans, the bacteria is thought to be passed through skin and nasal mucosa (WHO). One study has demonstrated that large numbers of the bacteria can be found on the skin of infected persons, providing a possible means of transmission (Job). Mycobacterium leprae could also be passed through nasal mucosa like the closely related Mycobacterium tuberculosis (Nature).

Infectious dose, incubation, and colonization

Mycobacterium leprae is not able to be cultured in the lab, which can hinder studies of infectious dose and incubation, however some sources provide estimates for these categories (Review). With a doubling time of 14 days (Shephard), Mycobacterium leprae has the longest doubling time of any studied bacteria (Nature). The World Health Organization states that Mycobacterium leprae has an incubation period of an average 5 years. Humans and armadillos are currently the only known reservoirs of the bacteria, with infected humans accounting for up to 7 billion organisms per gram of tissue (WHO). Mycobacterium leprae mostly lives in the extremities and facial region within macrophages and Schwann cells of the peripheral nervous system (Nature).

Epidemiology

Map of new leprosy cases annually (2010) From: Leprosymission.org [4]

Mycobacterium leprae is thought to have originated in East Africa and spread across the globe through human migratory trends, reaching the Western world within the last 500 years (Monot). In 2012, the World Health Organization recorded a prevalence of approximately 180,000 cases (WHO). Through eradication efforts, the total number of cases worldwide has decreased, yet the number of new cases each year has remained consistent (Review). Mortality is difficult to measure with leprosy, as the infection is not the immediate cause of death in many cases (WHO).

Virulence factors

Iron utilization

Although some genes from the closely related bacteria that causes tuberculosis have been deleted in Mycobacterium leprae, some iron utilization genes have been conserved to help the pathogen acquire nutrients for growth (Nature). NRAMP proteins can be coded for that allow transportation of iron into the macrophage for survival (Gruenheid).

Waxy exterior

Bacteria of the Mycobacterium Genus are defined by their waxy exterior coat. In Mycobacterium leprae, the exterior allows for intake into the macrophage and into some dendritic cells. The terminal mannose caps on the waxy mycobacterial ligand, lipoarabinomannan, of the pathogen are recognized by the Pathogen Recognizing Receptor (PRR) of the macrophage to allow for phagocytosis (Brennan).

Macrophage invasion

Mycobacterium leprae survives and replicates in macrophages, dividing to approximately 100 organisms per cell (Hagge). The bacteria prevent phagosome and lysosome fusion to avoid degradation (Sibley). In the event that the bacteria are absorbed into the phagolysosome, Mycobacterium leprae has the ability to survive emission of reactive oxygen species (Review).

Schwann cell invasion

Drug resistance

Clinical features

Disfigurement after Mycobacterium leprae infection. From: Bio.davidson.edu [5]

Classification

Leprosy presents with a variety of clinical features based primary on the degree to which the host immune system responds to the infection (Review). In general, the disease leprosy is a result of the immune response to Mycobcaterium leprae invasion of the Schwann cells, which leads to demyelination neuropathy (Swift). Common results of the immune response are loss of sensation and disfiguration (Nature). Chronic inflammation can lead to this paralysis, specifically along the periphery, and can also affect facial regions, contributing to factors such as blindness (Review). Classification of leprosy is based of a five part system which divides patients by immune response. There are two polar categories and three borderline types which fall between the polar classifications. One polar type is called tuberculoid (TT). This type is marked by a high level of host immune response, delayed hypersensitivity, and bacilli in biopsied tissue. The other extreme is called lepromatous (LL). In this type of leprosy, there is no host resistance. Nodular lesions will form all over body, and when biopsied, they reveal globi, or bundles of bacilli. The remaining three types are borderline categories, being closer to one polar type or the other, or having marks of both polar types. These are borderline lepromatous (BL), mid-borderline (BB), and borderline tuberculoid (BT) (Ridley and Jopling).


Clinical manifestations can be divided into two major categories: Type 1 and Type 2 reactions.

Type 1

Borderline leprosy types (BL, BB, and BT) are included in this classification. The symptoms include lesions that are red and hardened, fluid accumulation in the periphery, sensory loss, and neuropathy. Symptoms develop gradually and may last for several weeks (Review).

Type 2

Erythema nodosum leprosum, or Type 2 reactions, affect multibacillary patients (LL and BL). In contrast to Type 1 reactions, symptoms develop suddenly, subside after a couple weeks, and may reoccur many times over a period of months. Tender, red lesions erupt on the face, extremities, and trunk. These patients may develop inflammation of the eyes leading to blindness and other complications. General muscle inflammation, joint inflammation, and orchitis may occur (Review).

Lucio Phenomenon

The Lucio Phenomenon is a rare form of symptoms that describes a rapid onset of inflammation of the blood vessel walls and anemia. Typically this rarity occurs in Mexican leprosy patients (Donner).

Diagnosis

Diagnosis is typically made upon recognition of acid-fast bacilli in a skin biopsy of a lesion (Review). As some patients have few lesions, scientists are looking for immunodiagnostic tests to explain neuropathy and other symptoms that may be unaccompanied by lesions (Nature). For instance, tuberculoid leprosy (TT) often produces few lesions, so the disease can misdiagnosed. In lepramatous (LL) cases, biopsy should be made from a nerve cell to rule out alternative diagnoses which might show similar symptoms and bacilli in tissue (Review).

Treatment

Before and after Multidrug Therapy (MDT) From: Stlukesleprosyhospital.org [6]

The current standard treatment for Mycobacterium leprae infection is a Multi-drug Treatment (MDT) which consists of corticosteroids and antimicrobials. For paucibacillary leprosy, rifampicin and dapsone are used, while rifampicin, clofazimine, and dapsone are used in multibacillary leprosy. Rifampicin, ofloxacin, and minocycline can be combined in single lesion paucibacillary leprosy. Oral prednisolone can be used in secondary complications such as neuropathy and eye problems. Drops can be used to dilate the eye and stimulate relaxation to help the healing process (WHO). However, scientists are discovering drug-resistant strains of Mycobacterium leprae, so precautions must be taken (Review). Minocycline or ofloxacin can be used in the event of a rifampicin allergy, resistance, or presence of a disease antagonistic to rifampicin (WHO. Interestingly, the disease can sometimes be self-limiting and cure itself independently of drug treatment (WHO, REVIEW).

Prevention

Vaccination

A proper vaccination for Mycobacterium leprae would provide protective immunity. One vaccine has shown positive results in protecting the inoculated person from infection. The M. bovis BCG vaccine proved effective in India (Zodpey) and Brazil (Cunhua).

Eradication attempts

Global efforts to eradicate leprosy has resulted in elimination of the disease from 119 of 122 countries thought to be highly affected (WHO). With proper prevention measures, early detection, and treatment, numbers of new cases would decrease and those already infected could be cured (Nature).

Immune Response

Protective immunity and susceptibility

Host defense

Bacterial evasion

References

1 Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.

Created by Gracen Conway, student of Tyrrell Conway at the University of Oklahoma.