Leprosy: Fear, Hope and Treatment

Shweta K

Leprosy is a slowly progressive disorder causing granulomatous
lesions and is characterized by anaesthetic skin lesions and thickening of
the superficial nerves with sensory changes.

According to world health organization, five countries – India,
Brazil, Indonesia, Mayanmar and Nigeria, together constitute vast majority
of leprosy cases, of which India accounts for about one-third of all registered
leprosy cases globally. Historically, leprosy was an incurable and disfiguring
disease. Lepers were shunned and sequestered in lepr colnies.Even people avoid
to see the lepers as they are having fear to get the disease but today  leprosy
is easily curable by multidrug antibiotic therapy (MDT) and other new emerging
drugs. Since the lack of awareness about disease leads people to falsely believe
that the disease is highly contagious and incurable.Aim of review is to draw
the attention of people about the facts of leprosy and its tereatment.

Introduction

Leprosy is also
known as Hansen’s disease as G.A. Hansen discovered its causative organism in
1874¹. Leprosy is a chronic infectious disease caused by an
acid-fast bacillus, Mycobacterium leprae, related to the tubercle
bacillus. This bacillus multiplies very lowly in the body, and not in all
culture media. Thus no vaccine is available. It is essentially a disease of
peripheral nerves, but it also affects the skin, eyes, mucosa of the upper
respiratory tract, muscle, bone and testes². The complex and unique cell wall that makes the mycobacterium
family difficult to destroy is apparently also the reason for the extremely
slow replication rate.Mycobacterium leprae is typically transmiteed in airborne
droplets produced by coughing,breathing, and sneezing. Disease can be
transmitted through direct contact with untreated leprosy patients who shed
numerous bacilli from damaged skin, nasal secretions and also from
materno-foetal across the placenta In the United States, 200-300 cases of
leprosy are reported each year, it is most common in warm, wet areas in the
tropics and subtropics. WHO estimated that 12 to 20 million people worldwide
have leprosy, the majorities are in India,
China and Africa.
India alone has
about 4 million leprosy patients². Leprosy can affect people of all
races all around the world. People with light skin have a greater tendency to
have the lepromatous form of leprosy and African blacks report a higher
incidence of the tuberculoid form of leprosy. In adults, the lepromatous type
of leprosy is more common in men than women, with a male-to-female ratio of
2:1. In children, the tuberculoid form predominates. Leprosy has a
bimodal age distribution, with peaks in those aged 10-14 and in those aged
35-44 years. Once infected with the mycobacteria, the average incubation period
is two to three years, but it can range from 6 months to 40 years or longer. In
90% of patients the first sign of the disease is a feeling of numbness, which
may precede skin lesions by a number of years. Temperature is the first
sensation lost, followed by light touch, pain and then deep pressure. Sensory
loss usually begins in the extremities. Historically, leprosy was an incurable and disfiguring disease.In
all ages has been considered one of the more despicable diseases, and victims
have been despised throughout history and kept in separate places (leper
colonies, sanitariums). Even today, most people with leprosy are shunned by
their neighbors and are held at arms length. Peoples have a great fear of this
disease. Today, leprosy is easily
curable by multidrug antibiotic therapy (MDT). Antibiotic treatment has
dramatically improved patient’s outcomes. The newer treatment
and therapies given the ray of hope to the patient of leprosy. Insight
of that, this paper reviews the topic including its incidences, clinical
features, types, diagnosis, treatments ans prognosis.

Incidences

In 1999, the world incidence of Hansen's disease was
estimated to be 640,000; and in 2000, 738,284 cases
were identified. In 1999, 108 cases occurred in the United States.
In 2000, the World Health Organization (WHO) listed 91
countries in which Hansen's disease is endemic, with India, Myanmar,
and Nepal
having 70% of cases. In 2002,
763,917 new cases were detected worldwide, and in that year the WHO listed Brazil, Madagascar,
Mozambique,
Tanzania
and Nepal
as having 90% of Hansen's disease cases.

Worldwide, one to two million people are
permanently disabled because of Hansen's disease. However, persons receiving
antibiotic treatment or having completed treatment are considered free of
active infection. India is the number one in leper cases, with Brazil second,
and Myanmar third. Hansen's disease is one of the infectious diseases tracked
passively by the Centers for Disease Control and
Prevention. There are decreasing numbers of cases worldwide,
according to recent figures from the World Health Organization (WHO) new cases
detected worldwide has decreased by approximately 107,000 cases or 21% from
2003 to 2004. This decreasing trend has been consistent for the past three
years.

Clinical features

The condition begins insidiously. Skin lesions may
develop anywhere of the body as a 
particular area with imapired sensation or hypopigmented macules,
frequently with loss of hair over the lesions or as nodule swith thickening of
cutaneous tissue.The lesions may be diffuse and discrete, may form large
plaques or indolent ulcers covered with seropurulent exudate.The condition
rarely affects the central nervous system³. Reactional states
are the most common complications. These states can result in permanent
neurologic sequelae, resulting in disability and deformity. Lepra
type I and II reactions usually affect patients. Type-I is boderline reaction, in this boderline groups are unstable and
may across the spectrum in either direction with upgrading/downgrading of
patient’s immune state.Type-II is Erythema nodosum leprosum(ENL), it occurs in
lepromatus patients after treatment.It is characterised by tender cutaneous
nodules, fever,irdocyclitis,synouitis and lymp node involvement.

Types of leprosy

There are several forms
of leprosy that range from the mildest indeterminate form to the most severe
lepromatous type. Depending on clinical features, leprosy is classified^3-5
into six forms.

1. Indeterminate leprosy (IL):

Develops as an early benign and unstable condition and give rise to ill-defined
hypopigmented macule.

2. Tuberculoid leprosy (TT):

Arbitrarily classified into 3types, macular, minor and major. Macule has
clear definite margins, minor are slightly raised particularly at the margin,
major are larger and more raised. Spontaneous resolution may occur in a few
years or it may progress to borderline or rarely lepromatous types.

3. Borderline tuberculoid (BT): 

Lesions are smaller and more numerous, disease may stay in this stage or
convert back to tuberculoid form, or progress.

4. Borderline borderline (BB):

Numerous, red, irregularly shaped plaques, sensory loss is moderate, disease
may stay in this stage, improve or worsen.

5. Borderline lepromatous (BL):

Numerous lesions of all kinds, plaques, macules, papules and nodules. Lesions
looking like inverted saucers are common, hair growth and sensation are usually
not impaired over the lesions.

6 .Lepromatous (LL):

Early symptoms include nasal stuffiness, discharge and bleeding, and swelling
of the legs and ankles. Left untreated, the following problems may occur:

Skin thickens over forehead, eyebrows and eyelashes are lost, nose becomes
misshapen or collapses, ear lobes thicken, and upper incisor teeth fall out,
eye involvement causing photophobia (light sensitivity), glaucoma and blindness,
skin on legs thickens and forms ulcers when nodules break down, testicles
shrivel causing sterility and enlarged breasts (males), internal organ infection
causing enlarged liver and lymph nodes, voice becomes hoarse due to involvement
of the larynx, slow scarring of peripheral nerves resulting in nerve thickening
and sensory loss, fingers and toes become deformed due to painless repeated
trauma.

Diagnosis

Leprosy has very
characteristic clinical features but the diagnosis must be confirmed by various
tests, because of the need for prolonged treatment with antibiotics^6-12.

1. Tissue smear testing

An incision is
made in the skin, and the scalpel blade is used to obtain fluid from a lesion.
The fluid is placed on a glass slide and stained by using the Ziehl-Neelson
acid-fast method to look for organisms. The bacterial index (BI) is then
determined.

2. Skin biopsy

The skin biopsy
sample should be examined for morphologic features and the presence of
acid-fast bacilli. Biopsy is useful for determining the morphologic index (MI),
which is used in the evaluation and treatment of patients. It is the number of
viable bacilli per 100 bacilli in the leprous tissue.

3. Sensory testing

Tactile and
temperature sensations should be tested. A wisp of cotton can be used to test
for anesthesia of the lesions.

4. Lepromin testing

This test indicates
host resistance to M leprae. It results do not confirm the diagnosis,
but they are useful in determining the type of leprosy.

To perform this
test, bacillary suspension is injected into the forearm. When the reaction is
assessed at 48 hours, it is called the Fernandez reaction and indicates delayed
hypersensitivity to antigens of M leprae or mycobacterium that cross
react. When the reaction is read at 3-4 weeks, it is called the Mitsuda reaction and indicates that the immune system is
capable of mounting an efficient cell-mediated response.

5. Polymerase chain reaction (PCR) analysis

PCR can be used
to detect and identify M leprae. The technique is used most often when
acid-fast bacilli are detected but clinical or histopathologic features are
atypical.

Treatment

Until recently, the most commonly used drug has been “diamino-diphenyl-sulphone”
(DDS or Dapsone). But because of the widespread incidence of Dapsone resistance
over recent years, the World Health Organization now recommends using several
drugs in combination for the treatment of leprosy. The most useful of these
are - Rifampicin, Clofazimine and Dapsone. This multi-drug-therapy (MDT) greatly
increases the cost of treatment, but also considerably reduces the length
of time a patient needs treatment. Emergency surgery may be necessary if a
patient with profound nerve inflammation presents with a nerve abscess or
loss of nerve function secondary to compression. Elective surgery may be required
for correction of lagophthalmos (i.e. inability to close the eye). Beside
with medical treatment prevention and other outpatient care is also required.
Household contacts of patients with lepromatous disease should be annually
monitored for 5 years after diagnosis. Children especially should be observed
for the development of disease. WHO recommends 2 years of follow-up for paucibacillary
disease and 5 years of follow-up for multibacillary disease. In patients taking
dapsone, the complete blood count should be checked at frequent intervals
early during the therapy and at less frequent intervals later during therapy.
Sensation and muscle strength in the hands, feet, and eyes should be checked
on a regular basis. Drugs used to treat leprosy are

Described below (Table no-1).

 (1) Antimicrobials^13-26
 

For drug
treatment purposes, infections are classified as paucibacillary or
multibacillary. Paucibacillary disease can be treated with a combination of
Dapsone (100mg) and Rifampicin (600mg once monthly) for 6 months, whereas
multibacillary disease requires triple-drug therapy Dapsone (100mg), Rifampicin
(600mg once monthly) and clofazimine (300mg once monthly) for 2yrs. They are
recommended bye WHO. Antimicrobial are used to eliminate organisms. The
first-line drugs are dapsone, rifampin, and clofazimine. Other antibiotics
include minocycline, ofloxacin, and clarithromycin²⁷.

(a) Dapsone
(Avlosulfon) - Acts by blocking folic acid synthesis. Dapsone half-life is 1-2
days^28-29. During dapsone therapy of lepromatous leprosy, ENL, often develops. Now used as part of a multidrug regimen
to treat leprosy. Plasma concentrations ranges from 0.4-1.2microgram/ml, after
24hrs of oral ingestion of its dose (100mg)³⁰.

(b) Rifampin
(Rifadin, Rimactane)- Bactericidal for M leprae.
Inhibits DNA-dependent RNA polymerase, interfering with bacterial RNA
synthesis. Usually given with dapsone to reduce the emergence of resistance
strains of leprae³¹. Macrocyclic ring has an important bearing on
the binding to RNA polymerase, while the aromatic nucleus plays a large part in
determining penetration into the bacteria³².

(c) Clofazimine (Lamprene)- It inhibits mycobacterial
growth by binding to GC-rich mycobacterial DNA³³.Weakly bactericidal
against M leprae. Eosinophilic enteritis has been described as an
adverse reaction to the drug^34-38.

(2) Corticosteroids

These are
important anti-inflammatory agents used in the treatment of reactional leprosy.
Corticosteroids are the reliable only in the treatment of reversal reactions.
These medications can be used to treat leprosy reactions when a risk of
neurological deficits exists or when lesions occur in cosmetically important
places. They can also be used to treat ENL.

(a) Prednisone (Deltasone )- May
decrease inflammation by reversing increased capillary permeability and
suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses
lymphocytes and antibody production.

(3) Immunomodulators

These agents are
used to modify the immune system response to diverse stimuli.

(a) Thalidomide
(Thalomid) - Immunomodulatory
agent that may suppress excessive production of tumor necrosis factor-alpha
(TNF-alpha) and down-regulates selected cell-surface adhesion molecules
involved in leukocyte migration. Can be used to treat recurrent or refractory
ENL.

Prognosis

The prognosis
depends on the stage of disease. In borderline cases, the disease has the
potential to be downgraded to LL; these patients may have nerve damage. Even
with corticosteroid treatment, neuritis may not be curable.The
prognosis also depends on the patient’s access to therapy, the patient’s
compliance, and the early initiation of treatment.

Discussion

The main
challenges in the eradication of Hansen's disease are in reaching populations
that have not yet received multidrug therapy services, improving detection of
the disease, providing patients with high-quality services and affordable
drugs, and fighting social taboos about the disease where patients are
considered to be "unclean", or "cursed by God" and
outcasts. disease where patients are considered to be "unclean", or
"cursed by God" and outcasts. The last issue is important to address,
because in such societies, patients may be forced to hide their condition (and
thus not to seek treatment) in order not to be discriminated against, since the
lack of awareness about Hansen's disease leads people to falsely believe that
the disease is highly contagious and incurable.

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Table 1: Drugs for the treatment of leprosy with their dose as per WHO.

About Authors

Shweta K^*, Darshan D,  Satyaendra S.

Lecturers, Smriti college of pharmaceutical education, Indore

Shweta K

**For Correspondence

Smriti College Of Pharmaceutical Education, 4/1 Piplia Kumar Kakad, Mayakhedi
road, Indore (MP) 452010 T

Tel:  +91-731-2802262 Fax: +91-731-2802467, E-mail- kapoorscope@gmail.com,
Kapoor.sk@rediffmail.com

Darshan D

M. Pharm, Lecturer, Smriti college of pharmaceutical education,
Indore
E-mail- darshandubey@gmail.com

Satyaendra S

M. Pharm, Lecturer, Smriti college of pharmaceutical education,
Indore
E-mail-satyaendrascope@gmail.com