Download Leprosy: a review on elimination, reducing the disease

Lepr Rev (2015) 86, 307– 315
REVIEW
Leprosy: a review on elimination, reducing the
disease burden, and future research
CASANDRA CHAPTINI* & GILLIAN MARSHMAN*,**
* Flinders Medical Centre, Adelaide, South Australia,
Australia
** Flinders Medical Centre/Flinders Private Hospital,
Adelaide, South Australia, Australia
Accepted for publication 25 June 2015
Summary Leprosy, one of the oldest diseases known to man, is a stigmatising,
potentially disabling disease. Throughout history, leprosy has been associated with
fear, prejudice and immense social stigma. It remains one of the leading causes of
deformity and physical disability from an infectious disease. Tremendous advances in
leprosy control were made by the World Health Organization, and the ‘elimination of
leprosy’, defined as a decrease of disease prevalence to less than 1 case per 10,000
population, was achieved by 2000. However, the reality is that true ‘elimination’ is
yet to be achieved. Despite almost 30 years of effective multidrug treatment, the
prevalence and incidence of leprosy have plateaued since 2005. Moreover, new cases
with Grade 2 disability and new cases occurring in children remain unchanged since
2010, reflecting a failure in early leprosy detection, and indicating that transmission is
clearly continuing. This review examines the challenges of elimination, and proposes
further measures to reduce the disease burden, including future research possibilities.
Background
Leprosy, one of the oldest diseases known to man, is a stigmatising, potentially disabling
disease. It is a chronic, infectious disease caused by Mycobacterium leprae. Clinical
manifestations include skin, peripheral nerve, and eye lesions.1 Among communicable
diseases, leprosy is a leading cause of permanent physical disability.2 However, early
treatment is curative and averts disability. Leprosy is classified into paucibacillary (1-5 skin
patches), and multibacillary (greater than 5 patches). There are multiple social determinants
which impact upon leprosy control, as illustrated in Table 1.
To avoid drug resistance, multidrug treatment (MDT) consisting of dapsone, rifampicin
and clofazimine, was recommended by the World Health Organization (WHO) in 1981,
having a 98% cure rate.3,4
Correspondence to: Cassandra Chaptini, Flinders Medical Centre, Adelaide, South Australia, Australia
(e-mail: [email protected])
0305-7518/15/064053+09 $1.00
q Lepra
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C. Chaptini and G. Marshman
Table 1. Health determinants impacting on leprosy
Socioeconomic and emotional determinants
† Poverty and low income – leprosy is associated with poverty due to a multitude of factors, including lower
education, less access to health care services, lower income for required medications, poorer housing and increased
overcrowding
† Social status – leprosy is associated with a lower socioeconomic status for reasons such as lower income, poorer
education, and reduced access to health care services
† Education – low literacy levels and lack of education are associated with a higher rate of leprosy due to reduced
education around medical issues and an association with reduced income.
† Social stigma – leprosy is associated with a high social stigma, which causes a delay in diagnosis and treatment,
and increased disabilities
† Migration – migration of people (refugees, nomads, migrant workers and resettlers) from endemic leprosy areas to
low-endemic areas may cause re-emergence of disease
Environmental determinants
† Housing and clustering – leprosy is transmitted from person-to-person via close-contact (hypothesised to
be via respiratory droplets), and transmission of leprosy is highly associated with overcrowding and clustering
of people
† Water and sanitation – inadequate water and poor sanitation and hygiene may increase leprosy transmission
† Access to health services – poor access to health services causes a delay in treatment and can hinder treatment
adherence
† Disasters and conflicts – increases rate of leprosy due to increased migration and the breakdown of health care
systems
† Employment and working conditions – poor working conditions may increase leprosy transmission if
overcrowding and poor hygiene is present
Biological determinants
† Gender – there is an increased risk of leprosy in males, however there is a higher rate of morbidity and
complication in females (possibly due to increased stigmatisation)
† Genetics – there is evidence that not all people who are infected with Mycobacterium leprae develop leprosy.
Genetic factors are thought to be influential, based on the observation of clustering of leprosy around certain
families.
In the initial 3 years of MDT, the global leprosy prevalence reduced by a remarkable
45%5 sparking WHO’s governing body, the World Health Assembly, to pass a resolution
in 1991 to ‘eliminate leprosy as a public health problem by the year 2000.’6 The elimination
of leprosy, defined as a decrease of disease prevalence to less than 1 case per 10,000
population, was achieved by 2000. By 2006, all but six countries accomplished
national elimination.5 In 2013, 96% of new cases globally were detected in only 14
countries (Figure 1).5
Despite almost 30 years of effective MDT, the prevalence and incidence of leprosy have
plateaued since 2005 (Figure 2A).5
Moreover, new cases with Grade 2 disability (G2D) remain unchanged in 2013 compared
to 2010, reflecting a failure in early leprosy detection (Figure 2B).5
Additionally, new cases occurring in children have not reduced, reported at 9.2% in
2013,5 indicating transmission is clearly continuing.7
DEFINING ELIMINATION AND CONTROL
The World Health Organization defines, disease elimination as the reduction of infection
incidence to zero, and disease control as the reduction of disease incidence to a locally
Leprosy: a review on elimination
309
Figure 1. Global leprosy prevalence rates.
Data reported to WHO as of January 2012. Source: World Health Organisation7.
A
800,000
700,000
Number of new
cases/100,000
population (proxy
measure for
incidence)
Number of people
600,000
500,000
400,000
Number of
registered cases/
100,000 population
(proxy measure for
prevalence)
300,000
200,000
100,000
0
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Year
B
20000
18000
16000
Number of people
14000
12000
Number of new
cases with G2D*/
100,000 population
10000
8000
Number of relapsed
cases/100,000
population
6000
4000
2000
0
2007
2008
2009
2010
2011
2012
2013
Year
Figure 2. Global burden of leprosy disease. (A) Incidence and prevalence of leprosy. (B) New cases with Grade 2
disability (G2D)* and number of relapsed cases. *Grade 2 disability (G2D) is defined as visible deformity or
damage present, or severe visual impairment. Graphs were created from data reported by WHO5,8 – 17.
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C. Chaptini and G. Marshman
acceptable level.18 However, WHO defined leprosy elimination in terms of prevalence
reduction, which is essentially a control target.19 Nonetheless, it was anticipated that a
decrease in prevalence would ultimately lead to elimination.20 A fundamental assumption of
the elimination strategy was that MDT reduced M. leprae transmission.21 However,
unfortunately, there is no substantial evidence available supporting this.19,22 – 25 Evaluating
the effect of MDT on transmission is difficult due to many factors. Firstly, leprosy has a long,
variable incubation period, ranging from 2 – 20 years, and laboratory tools to detect leprosy in
the early stages are lacking.1 Secondly, decreases in case detection have other causes,
including the bacille Calmette-Guérin BCG) vaccination.26 Finally, variable control
measures used over time obscures interpretation of trend data.19
THE CHALLENGES OF ELIMINATION
Although the goal was to eliminate leprosy as a public health problem, the terminology
misled many people, including policy makers to believe that the goal was complete
elimination.3 This may partly explain the reduction in leprosy programme funding, the
decrease of academic work on leprosy, and why leprosy rarely features in medical school
curriculum, even in endemic countries.3
Although WHO abandoned the ‘elimination’ target in 2007, national leprosy rates are still
emphasised, which may have unintended damaging consequences, as demonstrated in India
for example.3,19,27 The pressure on outstanding countries to meet the elimination target by
2005 resulted in India meeting the target, however independent studies showed many
undiagnosed patients, and it was found that measures were adopted to ensure fewer patients
were registered, including not registering single lesion cases and not tracing contacts.3,28
Subsequently, India has reported approximately 130,000 new cases a year, keeping it in the
‘eliminated’ category.3 However, from 2004– 2007 new case detection dropped by 75%, but
the proportion of G2D cases increased by 38%.14,16,19 This indicates less active case finding,
which may partly be due to a decreased incentive to find new cases, and has a devastating
effect on leprosy morbidity.3,28,29
Although it is important to set targets to provide direction for national programmes and
secure political commitment, the targets used are imperative. Evidence has demonstrated that
disability-based targets encourage early diagnosis and treatment, and prevent morbidity.30,31
Hence, there has been a shift from placing importance solely on ‘elimination’ and total new
cases found, to emphasising disability rates, for instance, new cases of G2D.
Unfortunately, the celebration of the leprosy progress may have resulted in a loss of
political commitment.33 Funding for leprosy programmes has been reducing by 5% per year
globally, for the past 5 years.3 Currently, few countries have a surveillance-response system
to provide epidemiological data, and implement required interventions. Moreover, many
leprosy programmes have been left unsupported and the skills in diagnosis and management
have dwindled.3 In some countries where marked success has occurred, unfortunately there
has been an increase in multibacillary and disability cases.3
In the face of other competing priorities (e.g. HIV, malaria, TB), a major challenge is for
leaders across all sectors to reaffirm commitment and allocate increased resources at a global
and national level. Where facilities are weak, sharing facility control programmes for other
diseases should be considered.33 There is an urgent need to rebuild and sustain leprosy
expertise, and to develop strategies globally and nationally, in collaboration with partners,
to augment training programmes. Additionally, national efforts are needed to involve
Leprosy: a review on elimination
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dermatologists in the leprosy control programme to sustain high-quality leprosy services. To
achieve this, it is vital that partnerships are solidified between governments, non-government
organisations, the private sector, international agencies, professional associations and people
affected by leprosy.
FUTURE MEASURES FOR REDUCING THE DISEASE BURDEN
Contact surveillance
The risk of acquiring leprosy for individuals living in households with multibacillary patients
is 5 – 10 times higher, and with paucibacillary patients 2 –3 times higher, than in people not
living in such households.32 Unrecognised cases and subclinical infections in contacts
contribute a significant proportion of all new leprosy cases.32 Hence, if case detection
campaigns and mandatory contact tracing programmes were implemented nationally, this
would undoubtedly reduce the disease burden.
Immunoprophylaxis
Ideally, disease control is best obtained by an effective vaccine. BCG vaccine, although
imperfect, is used globally, with 85% of the world’s infants receiving it.32 The protection
imparted by BCG against leprosy is highly variable for poorly understood reasons.26,34
A meta-analysis showed an overall protective effect of 26% [95% confidence interval (CI):
14 –37%] in experimental studies, and of 61% [95% CI 51 –70%] in observational studies.26,32
In recent studies it was demonstrated that an additional dose of BCG was more protective
compared with a single dose, with protection lasting for decades.26 It has been proposed that an
additional dose of BCG be given for all at risk groups in high endemic areas.26
Chemoprophylaxis
There is much evidence for the use of chemoprophylaxis in asymptomatic contacts.32,35 – 40 A
meta-analysis of seven randomised-controlled trials (RCTs) demonstrated that chemoprophylaxis provided 60% protection against leprosy.40 Rifampicin has an additive effect to
BCG. An RCT showed that individually BCG and rifampicin provided 57% (95% CI:
24 –75%) and 58% (95% CI: 30-74%) protection respectively, but the combined strategies
had a protective effect of 80% (95% CI: 50-92%).38 It has been hypothesised that if national
programmes gave one dose of rifampicin and BCG to asymptomatic contacts, it would
prevent many potential cases and reduce ongoing transmission.36,37
Preventing drug resistance
Several reports of rifampicin, dapsone and ofloxacin resistance have been published.32,41 If
chemoprophylaxis were to be introduced, avoiding drug resistance is imperative, and
stringent longitudinal observation is required so that timely measures to combat resistance
can be developed.42,32
Globally, more and more relapses are being reported.5,8 – 17 Relapse suggests treatment
failure, caused by inadequate or irregular treatment.5 It is vital to continuously monitor
relapse cases in relation to treatment completion and drug resistance in all national
programmes.
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Treatment adherence is a major factor in drug resistance. In developing countries,
patients’ treatment is often interrupted due to drug shortage or poor access to health services.
‘Accompanied MDT’ has been advised by WHO to be considered in these settings, whereby
a patient is given the entire treatment course on diagnosis, and nominates someone to
accompany them to aid in understanding the treatment.32 Many patients also stop treatment
due to lepra reactions, which are immunologically mediated episodes of inflammation. It is
imperative that health care workers and the community remain educated via leprosy
programmes, and know not to cease MDT during these reactions.
Disability prevention and rehabilitation
Even after effective treatment, long-term morbidity and disability is problematic. Up to 60%
of patients have peripheral nerve damage at diagnosis.3,50,51 Ongoing education of health care
workers and the community is vital to prevent damage to hands, feet and eyes in those with
peripheral neuropathy.3,51 Appropriate referral is important for acute complications and
improved rehabilitation services are needed for those with disability to improve quality of life.
Reducing leprosy stigmatisation
The stigma of leprosy is still profound in many communities, and increased community
awareness is necessary to motivate affected individuals to seek treatment. It is essential for
programmes to foster partnerships with people affected by leprosy. Key actions to strengthen
community involvement, and enable early disease presentation are outlined in Table 2.
Increased community participation will aid in operationalising policy formulation and
achieving successful policy implementation, to increase case finding, improve treatment
adherence, and ultimately prevent disability.
Table 2. Strengthening community action and reducing stigmatisation
Goal
Action
† Increased involvement of
persons affected by leprosy
† Advocate that people with leprosy provide information to the general public
and media, to overcome educational, and cultural and social barriers
† Encourage people with leprosy to be involved in public policy
† Support empowerment workshops
† Increase community education to address myths and misconceptions
which generate discrimination and human rights abuses
† Use a “people first” language i.e. “persons with leprosy,” rather than
negative terms, such as “lepper”
† Encourage information, education and communication
† Display of posters about leprosy in public places
† Enlist the support of others to spread positive messages about leprosy,
including community leaders, teachers, religious authorities and traditional
practitioners
† Place global pressure on countries to abolish laws containing discriminatory
clauses against persons with leprosy
† Support groups for women
† Identify female leaders with leprosy to act as role models
† Include all woman in empowerment workshops
† Incorporate women in delivery systems
† Decreased community
stigma of leprosy
† Improved community
education
† Abolition of all
discriminatory laws
† Decreased stigmatisation
and discrimination
amongst woman
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FUTURE RESEARCH
Over a century after its’ discovery, M. leprae still cannot be cultured in vitro, and significant
gaps persist in our understanding of its biology.43 The mode of transmission and period of
infectivity remains unknown. It is undetermined if leprosy is transmitted during incubation or
if there are healthy carriers. It was demonstrated that DNA from M. leprae exists in the nasal
passages of asymptomatic individuals, however further research is needed.44 Also, effective
screening tools are lacking, so early treatment depends on self-identification or a high-index
of suspicion by clinicians.
The relevance of non-human and environmental reservoirs is yet to be studied.45 – 49
Leprosy has been found in wild armadillos, and non-human primates, however the
significance of this in human infection is unknown.47 – 49 Several studies demonstrated an
environmental reservoir in the soil of endemic regions.45,46
These limitations massively hinder effective leprosy control, and further research is
needed to develop new diagnostic and epidemiologic tools. Additionally, research into the
logistics of prophylaxis implementation and cost – effectiveness of such policies would be
beneficial, as would the development of new chemoprophylactic and immunoprophylactic
regimens.
Conclusion
Elimination of a disease is truly difficult to achieve, especially one such as leprosy, which has
such a long, variable incubation period and much remains unknown about its biology.
Leprosy, an enigmatic disease, is one of the oldest diseases known to man, yet dramatic gaps
remain in our basic understanding of this disease, including transmission and pathogenesis.
Although substantial progress has been made in providing treatment to those with leprosy,
further developments are needed. Future progress toward eradicating leprosy is dependent on
a better understanding of the disease transmission and new tools to interrupt it. Hopefully, the
progress made can be maintained and further advanced by the political will of governments,
and ongoing research into this disease and its treatment. We urge all countries, governments,
stakeholders, and individuals to reaffirm their commitment to reducing the burden of one of
the world’s most devastating diseases, so that someday we can say leprosy is truly eliminated.
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