Leprosy

Leprosy (from the Greek lepid, meaning scales on a fish), or Hansen's disease, is a chronic
disease caused by the bacterium Mycobacterium leprae. Leprosy is primarily a granulomatous
disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions are the
primary external symptom. Left untreated, leprosy can be progressive, causing permanent
damage to the skin, nerves, limbs and eyes. Contrary to popular belief, leprosy does not actually
cause body parts to simply fall off.

Historically, leprosy has affected mankind since at least 600 BC, and was well-recognized in the
civilizations of ancient China, Egypt and India. In 1995, the World Health Organization (WHO)
estimated that between two and three million people were permanently disabled because of
leprosy. Although the forced quarantine or segregation of patients is unnecessary—and can be
considered unethical—a few leper colonies still remain around the world, in countries such as
India, Japan, Egypt, Nepal and Vietnam. It is now commonly believed that many of the people
who were segregated into these communities were presumed to have leprosy, when they actually
had syphilis. Leprosy, which is not highly infectious, as approximately 95% of people are
immune and after only a couple of days on treatment sufferers are no longer infectious, would
not have spread through a community, whereas syphilis, which has similar symptoms, is
contagious.

The age-old social stigma associated with the advanced form of leprosy lingers in many areas,
and remains a major obstacle to self-reporting and early treatment. Effective treatment for
leprosy appeared in the late 1930s with the introduction of dapsone and its derivatives. However,
leprosy bacilli resistant to dapsone gradually evolved and became widespread, and it was not
until the introduction of multidrug therapy (MDT) in the early 1980s that the disease could be
diagnosed and treated successfully within the community.[citation needed]

Characteristics
Cutaneous leprosy lesions on a patient's thigh.

The clinical symptoms of leprosy vary but primarily affect the skin, nerves, and mucous
membranes. Patients with this chronic infectious disease are classified as having paucibacillary
Hansen's disease (tuberculoid leprosy), multibacillary Hansen's disease (lepromatous
leprosy), or borderline leprosy.

Contrary to popular belief, Hansen's bacillus does not cause rotting of the flesh; rather, a long
investigation by Paul Brand yielded that insensitivity in the limbs extremities was the reason why
unfelt wounds or lesions, however minute, lead to undetected deterioration of the tissues, the
lack of pain not triggering an immediate response as in a fully functioning body. Recently,
leprosy has also emerged as a problem in HIV patients on antiretroviral drugs.

Classification
There is some confusion over classification because the WHO replaced an older, more
complicated classification system with a simpler system that identifies two subtypes of leprosy:
paucibacillary and multibacillary. The older system included six categories: Indeterminate
Leprosy, Borderline Tuberculoid Leprosy, Midborderline Leprosy, Borderline Lepromatous
Leprosy, Lepromatous Leprosy, and Tuberculoid Leprosy.

Paucibacillary leprosy encompasses indeterminate, tuberculoid, and borderline tuberculoid

leprosy. It is characterized by one or more hypopigmented skin macules and anaesthetic patches,
where skin sensations are lost because of damaged peripheral nerves that have been attacked by
the human host's immune cells.

Multibacillary leprosy includes midborderline, borderline lepromatous, and lepromatous leprosy.

It is associated with symmetric skin lesions, nodules, plaques, thickened dermis, and frequent
involvement of the nasal mucosa resulting in nasal congestion and epistaxis (nose bleeds) but
typically detectable nerve damage is late.

Borderline leprosy is of intermediate severity and is the most common form. Skin lesions
resemble tuberculoid leprosy but are more numerous and irregular; large patches may affect a
whole limb, and peripheral nerve involvement with weakness and loss of sensation is common.
This type is unstable and may become more like lepromatous leprosy or may undergo a reversal
reaction, becoming more like the tuberculoid form.

Cause
 Main article: Mycobacterium leprae

Mycobacterium leprae, the causative agent of leprosy. As acid-fast bacteria, M. leprae appear red
when a Ziehl-Neelsen stain is used.

Mycobacterium leprae is the causative agent of leprosy. An intracellular, acid-fast bacterium, M.

leprae is aerobic and rod-shaped, and is surrounded by the waxy cell membrane coating
characteristic of Mycobacterium species.

Due to extensive loss of genes necessary for independent growth, M. leprae is unculturable in the
laboratory, a factor which leads to difficulty in definitively identifying the organism under a strict
interpretation of Koch's postulates. The use of non-culture-based techniques such as molecular
genetics has allowed for alternative establishment of causation.

Pathophysiology
The exact mechanism of transmission of leprosy is not known: prolonged close contact and
transmission by nasal droplet have both been proposed, and, while the latter fits the pattern of
disease, both remain unproven The only other animals besides humans known to contract leprosy
are the armadillo, chimpanzee, sooty mangabey, and cynomolgus macaque. The bacterium can
also be grown in the laboratory by injection into the footpads of mice. There is evidence that not
all people who are infected with M. leprae develop leprosy, and genetic factors have long been
thought to play a role, due to the observation of clustering of leprosy around certain families, and
the failure to understand why certain individuals develop lepromatous leprosy while others
develop other types of leprosy It is estimated that due to genetic factors, only 5 percent of the
population is susceptible to leprosy. This is mostly because the body is naturally immune to the
bacteria, and those persons who do become infected are experiencing a severe allergic reaction to
the disease. However, the role of genetic factors is not entirely clear in determining this clinical
expression. In addition, malnutrition and prolonged exposure to infected persons may play a role
in development of the overt disease.

The incubation period for the bacteria can last anywhere from two to ten years.

The most widely held belief is that the disease is transmitted by contact between infected persons
and healthy persons. In general, closeness of contact is related to the dose of infection, which in
turn is related to the occurrence of disease. Of the various situations that promote close contact,
contact within the household is the only one that is easily identified, although the actual
incidence among contacts and the relative risk for them appear to vary considerably in different
studies. In incidence studies, infection rates for contacts of lepromatous leprosy have varied from
6.2 per 1000 per year in Cebu, Philippines to 55.8 per 1000 per year in a part of Southern India.
Two exit routes of M. leprae from the human body often described are the skin and the nasal
mucosa, although their relative importance is not clear. It is true that lepromatous cases show
large numbers of organisms deep down in the dermis. However, whether they reach the skin
surface in sufficient numbers is doubtful. Although there are reports of acid-fast bacilli being
found in the desquamating epithelium (sloughing of superficial layer of skin) of the skin,
Weddell et al had reported in 1963 that they could not find any acid-fast bacilli in the epidermis,
even after examining a very large number of specimens from patients and contacts. In a recent
study, Job et al found fairly large numbers of M. leprae in the superficial keratin layer of the skin
of lepromatous leprosy patients, suggesting that the organism could exit along with the
sebaceous secretions.

The importance of the nasal mucosa was recognized as early as 1898 by Schäffer, particularly
that of the ulcerated mucosa The quantity of bacilli from nasal mucosal lesions in lepromatous
leprosy was demonstrated by Shepard as large, with counts ranging from 10,000 to 10,000,000
Pedley reported that the majority of lepromatous patients showed leprosy bacilli in their nasal
secretions as collected through blowing the nose. Davey and Rees indicated that nasal secretions
from lepromatous patients could yield as much as 10 million viable organisms per day

The entry route of M. leprae into the human body is also not definitely known. The two seriously
considered are the skin and the upper respiratory tract. While older research dealt with the skin
route, recent research has increasingly favored the respiratory route. Rees and McDougall
succeeded in the experimental transmission of leprosy through aerosols containing M. leprae in
immune-suppressed mice, suggesting a similar possibility in humans. Successful results have
also been reported on experiments with nude mice when M. leprae were introduced into the nasal
cavity by topical application. In summary, entry through the respiratory route appears the most
probable route, although other routes, particularly broken skin, cannot be ruled out. The CDC
notes the following assertion about the transmission of the disease: "Although the mode of
transmission of Hansen's disease remains uncertain, most investigators think that M. leprae is
usually spread from person to person in respiratory droplets."

In leprosy both the reference points for measuring the incubation period and the times of
infection and onset of disease are difficult to define; the former because of the lack of adequate
immunological tools and the latter because of the disease's slow onset. Even so, several
investigators have attempted to measure the incubation period for leprosy. The minimum
incubation period reported is as short as a few weeks and this is based on the very occasional
occurrence of leprosy among young infants. The maximum incubation period reported is as long
as 30 years, or over, as observed among war veterans known to have been exposed for short
periods in endemic areas but otherwise living in non-endemic areas. It is generally agreed that
the average incubation period is between 3 and 5 years.

Treatment
MDT patient packs and blisters

Until the development of dapsone, rifampicin, and clofazimine in the 1940s, there was no
effective cure for leprosy. However, dapsone is only weakly bactericidal against M. leprae and it
was considered necessary for patients to take the drug indefinitely. Moreover, when dapsone was
used alone, the M. leprae population quickly evolved antibiotic resistance; by the 1960s, the
world's only known anti-leprosy drug became virtually useless.

The search for more effective anti-leprosy drugs than dapsone led to the use of clofazimine and
rifampicin in the 1960s and 1970s. Later, Indian scientist Shantaram Yawalkar and his colleagues
formulated a combined therapy using rifampicin and dapsone, intended to mitigate bacterial
resistance. Multidrug therapy (MDT) and combining all three drugs was first recommended by a
WHO Expert Committee in 1981. These three anti-leprosy drugs are still used in the standard
MDT regimens. None of them are used alone because of the risk of developing resistance.

Because this treatment is quite expensive, it was not quickly adopted in most endemic countries.
In 1985 leprosy was still considered a public health problem in 122 countries. The 44th World
Health Assembly (WHA), held in Geneva in 1991 passed a resolution to eliminate leprosy as a
public health problem by the year 2000 — defined as reducing the global prevalence of the
disease to less than 1 case per 100,000. At the Assembly, the World Health Organization (WHO)
was given the mandate to develop an elimination strategy by its member states, based on
increasing the geographical coverage of MDT and patients’ accessibility to the treatment.

The WHO Study Group's report on the Chemotherapy of Leprosy in 1993 recommended two
types of standard MDT regimen be adopted. The first was a 24-month treatment for
multibacillary (MB or lepromatous) cases using rifampicin, clofazimine, and dapsone. The
second was a six-month treatment for paucibacillary (PB or tuberculoid) cases, using rifampicin
and dapsone. At the First International Conference on the Elimination of Leprosy as a Public
Health Problem, held in Hanoi the next year, the global strategy was endorsed and funds
provided to WHO for the procurement and supply of MDT to all endemic countries.
MDT anti-leprosy drugs: standard regimens

Between 1995 and 1999, WHO, with the aid of the Nippon Foundation (Chairman Yōhei
Sasakawa, World Health Organization Goodwill Ambassador for Leprosy Elimination), supplied
all endemic countries with free MDT in blister packs, channelled through Ministries of Health.
This free provision was extended in 2000 with a donation by the MDT manufacturer Novartis,
which will run until at least the end of 2010. At the national level, non-government organizations
(NGOs) affiliated to the national programme will continue to be provided with an appropriate
free supply of this WHO supplied MDT by the government.

MDT remains highly effective and patients are no longer infectious after the first monthly dose.
It is safe and easy to use under field conditions due to its presentation in calendar blister packs.
Relapse rates remain low, and there is no known resistance to the combined drugs. The Seventh
WHO Expert Committee on Leprosy, reporting in 1997, concluded that the MB duration of
treatment—then standing at 24 months—could safely be shortened to 12 months "without
significantly compromising its efficacy."

Persistent obstacles to the elimination of the disease include improving detection, educating
patients and the population about its cause, and fighting social taboos about a disease for which
patients have historically been considered "unclean" or "cursed by God" as outcasts. Where
taboos are strong, patients may be forced to hide their condition (and avoid seeking treatment) to
avoid discrimination. The lack of awareness about Hansen's disease can lead people to falsely
believe that the disease is highly contagious and incurable.

The ALERT hospital and research facility in Ethiopia provides training to medical personnel
from around the world in the treatment of leprosy, as well as treating many local patients.
Surgical techniques, such as for the restoration of control of movement of thumbs, have been
developed there.
Prevention
A single dose of rifampicin is able to reduce the rate of leprosy in contacts by 57% to 75%.

BCG is able to offer a variable amount of protection against leprosy as well as against
tuberculosis.

Epidemiology

World distribution of leprosy, 2003.

Worldwide, two to three million people are estimated to be permanently disabled because of
Leprosy. India has the greatest number of cases, with Brazil second and Burma third.

In 1999, the world incidence of Hansen's disease was estimated to be 640,000; 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. India,
Myanmar and Nepal contained 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.

According to recent figures from the WHO, new cases detected worldwide have decreased by
approximately 107,000 cases (or 21%) from 2003 to 2004. This decreasing trend has been
consistent for the past three years. In addition, the global registered prevalence of HD was
286,063 cases; 407,791 new cases were detected during 2004.

Hansen's disease is tracked by the Centers for Disease Control and Prevention (CDC). Its
prevalence in the United States is believed to be rising and underreported. Although the number
of cases worldwide continues to fall, pockets of high prevalence continue in certain areas such as
Brazil, South Asia (India, Nepal), some parts of Africa (Tanzania, Madagascar, Mozambique)
and the western Pacific.
Risk groups

At highest risk are those living in endemic areas with poor conditions such as inadequate
bedding, contaminated water and insufficient diet, or other diseases (such as HIV) that
compromise immune function. Recent research suggests that there is a defect in cell-mediated
immunity that causes susceptibility to the disease. Less than ten percent of the world's population
is actually capable of acquiring the disease[citation needed]. The region of DNA responsible for this
variability is also involved in Parkinson's disease[citation needed], giving rise to current speculation that
the two disorders may be linked in some way at the biochemical level. In addition, men are twice
as likely to contract leprosy as women.

According to The Leprosy Mission Canada, most people – about 95% of the population – are
naturally immune.

Disease burden

Although annual incidence—the number of new leprosy cases occurring each year—is important
as a measure of transmission, it is difficult to measure in leprosy due to its long incubation
period, delays in diagnosis after onset of the disease and the lack of laboratory tools to detect
leprosy in its very early stages.

Instead, the registered prevalence is used. Registered prevalence is a useful proxy indicator of the
disease burden as it reflects the number of active leprosy cases diagnosed with the disease and
retrieving treatment with MDT at a given point in time. The prevalence rate is defined as the
number of cases registered for MDT treatment among the population in which the cases have
occurred, again at a given point in time.

New case detection is another indicator of the disease that is usually reported by countries on an
annual basis. It includes cases diagnosed with onset of disease in the year in question (true
incidence) and a large proportion of cases with onset in previous years (termed a backlog
prevalence of undetected cases). The new case detection rate (NCDR) is defined by the number
of newly detected cases, previously untreated, during a year divided by the population in which
the cases have occurred.

Endemic countries also report the number of new cases with established disabilities at the time of
detection, as an indicator of the backlog prevalence. However, determination of the time of onset
of the disease is generally unreliable, is very labour-intensive and is seldom done in recording
these statistics.
Maternal health care is a concept that encompasses family planning, preconception, prenatal, and postnatal care.
Goals of preconception care can include providing education, health promotion, screening and interventions for
women of reproductive age to reduce risk factors that might affect future pregnancies. Prenatal care is the
comprehensive care that women receive and provide for themselves throughout their pregnancy. Women who begin
prenatal care early in their pregnancies have better birth outcomes than women who receive little or no care during
their pregnancies. Postnatal care issues include recovery from childbirth, concerns about newborn care, nutrition,
breastfeeding, and family planning. Most women do not have access to the health care and sexual health education
services that they need. In many developing countries, complications of pregnancy and childbirth (mainly at the
level of preconception and prenatal care) are the leading causes of death among women of reproductive age. More
than one woman dies every minute from such causes; 585,000 women die every year (WHO). Less than one percent
of these deaths occur in developed countries, demonstrating that they could be avoided if resources and services
were available (WHO). Any woman can experience sudden and unexpected complications during pregnancy,
childbirth, and just after delivery. Although high-quality, accessible health care has made maternal death a rare event
in developed countries, these complications can often be fatal in the developing world.

Consequently, mothers in developing nations die in childbirth at a hundred or more times the rate in developed
nations (MDG). Access to emergency obstetric care, the most important remedy for women in these regions is not
highly regarded as a priority.

Factors that prevent women in developing countries from getting the health care they need include distance from
health services, cost (direct fees as well as the cost of transportation, drugs, and supplies), multiple demands on their
time, and women’s lack of decision-making power within the family. The poor quality of services, including poor
treatment by health providers, also makes some women reluctant to use services.

According to the World Health Report in 2004, bad maternal conditions account for the fourth leading cause of
women after HIV/AIDS, malaria, and tuberculosis. 99% of these deaths occur in low-income countries; while only 1
of 4,000 women have a chance of dying in pregnancy or childbirth in a developed nation, a woman in Sub-Saharan
Africa has a 1 in 16 chance of dying. Furthermore, maternal problems cause almost 20% of the total burden of
disease for women in developing countries.

Almost 50% of the births in developing countries take place without a skilled attendant to aid the mother and the
ratio is even higher in South Asia (UNICEF).

Proposed solutions

The World Bank estimated that a total of 3.00 US dollars per person a year can provide basic family planning,
maternal and neonatal health care to women in developing countries [1]. Many non-profit organizations have
programs educating the public and gaining access to emergency obstetric care for mothers in developing countries.

The services needed are said to include:

• doctor) at birth
Routine maternal care for all pregnancies, including a skilled attendant (midwife or
• Emergency treatment of complications during pregnancy, delivery and after birth
• Postpartum family planning and basic neonatal care
• Educating women and their communities about the importance of maternal health care,
and according women the social status to make health care decisions and seek medical
attention.
• Any form of education, even 6 years worth of education for girls can drastically improve
overall maternal health (UNICEF)
• Research on social and psychological factors affecting maternal healtDevelopment of
better interventions (and evaluations of interventions) for complex problems (e.g.,
behavioral, social, biological, cultural) arising in marginalized communities