Review
Leprosy now: epidemiology, progress, challenges, and
Lancet Infect Dis 2011;
11: 464–70
Department of Infectious
Disease Epidemiology, Faculty
of Epidemiology and
Population Health
(Prof L C Rodrigues PhD), and
Department of Clinical
Research, Faculty of Infectious
and Tropical Diseases
(Prof D N J Lockwood MD),
London School of Hygiene and
Tropical Medicine, London, UK
Correspondence to:
Prof Laura C Rodrigues, Faculty
of Epidemiology and Population
Health, London School of
Hygiene and Tropical Medicine,
Keppel St, London WC1E 7HT, UK
laura.rodrigues@lshtm.ac.uk
464
research gaps
Laura C Rodrigues, Diana N J Lockwood
Leprosy continues to be a challenge to health worldwide, with about 250 000 new cases being detected every year.
Despite widespread implementation of effective multidrug therapy, leprosy has not been eliminated. A third of newly
diagnosed patients have nerve damage and might develop disabilities, although the proportion varies according to
several factors, including level of self-care. Women who develop leprosy continue to be especially disadvantaged, with
rates of late diagnosis and disability remaining high in this subgroup. Leprosy was not a specified disease in the
Millennium Development Goals, but improvements in the other areas they cover, such as education and levels of
poverty, will help leprosy patients and services. We review data and make recommendations for research on diagnosis,
treatment, and prevention, such as further use of molecular analysis of the Mycobacterium leprae genome,
implementation of BCG vaccination, and administration of chemoprophylaxis to household contacts. We also suggest
development of tools for early diagnosis and detection of infection and nerve damage, and formulation of strategies
to manage the chronic complications of leprosy, such as immune-mediated reactions and neuropathy.
Introduction and the cost-effectiveness of offering chemoprophylaxis
Leprosy is the leading infectious cause of disability.1 are not simple. Research is needed, therefore, to inform
Prevalence has fallen substantially in the past 50 years,2 but future policies. New avenues for basic science and
transmission continues and leprosy remains a public health clinical research have been opened by sequencing the
problem.3 Various hindrances remain to reducing this genome of Mycobacterium leprae and genome-wide
prevalence further. The mode of transmission of leprosy is analysis of leprosy cases.9–11 Genomic data might be
not well understood, although it is probably person to useful in the development of drugs and vaccines against
person via nasal droplets.4 How many infected people leprosy. Health-care features that require research are
develop clinical disease and whether reactivation of past how to ensure equality in access to facilities for early
infections is important are unknown. Although making a diagnosis and to rehabilitation services, and ways to
clinical diagnosis is frequently straightforward, no good reduce stigma.
point-of-care test is available for confirming it. Delay in In this Review we discuss the epidemiology of leprosy
diagnosis can have important negative outcomes, such as and the progress in and challenges to control, and make
increased risk of nerve damage. Various factors contribute recommendations for research. The article is based on
to delay, but stigma is an important feature in many the review undertaken for the Disease-Specific Reference
cultures.5 Additionally, the immune responses and the Group on tuberculosis, leprosy and buruli ulcer (one of
mechanisms involved in nerve damage are not clearly the ten expert reference groups sponsored by the Special
understood; there is no predictive test for the extent of nerve Programme for Research and Training in Tropical
damage and no good evidence on the best treatment. Type 1 Diseases to assess the global research evidence on
and type 2 immune-mediated reactions continue to be infectious diseases of poverty). We also take into account
major complications, and affect around 30% of patients. the WHO worldwide strategy for reducing the burden of
WHO has set a target for reducing the number of cases disease related to leprosy,3 the decisions of its Technical
with grade 2 disability at diagnosis, but the feasibility of Advisory Group on Leprosy Control,6 and the research
reporting disability accurately needs to be assessed. The findings in leprosy from 2002–09 drawn together by the
integration of leprosy services into general health services International Federation of Anti-Leprosy Organisations
has led to a loss of skills in the diagnosis and management Technical Commission.5
of leprosy. WHO recommends multidrug therapy for
6 months in patients with paucibacillary disease (up to History of leprosy and leprosy control
five skin lesions) and for 12 months in patients with DNA analysis of M leprae strains suggests that this
multibacillary disease (more than five skin lesions).3 These bacterium originated in Africa and spread to Asia and
regimens might, however, be insufficient for patients with South America.9 Dapsone monotherapy was effective
lepromatous disease and high bacterial indices, and no and was started in the 1940s. Lifelong administration
alternative drug regimens are currently recommended.6 was required, however, and in the 1960s widespread
Drug resistance has not so far been an issue with resistance was reported.12 In 1981, WHO recommended
multidrug therapy,7 but monitoring is essential. that all patients should receive multidrug therapy
Various areas of research are a priority in the worldwide comprising rifampicin and dapsone, or rifampicin,
management of leprosy. Contacts of leprosy patients are dapsone, and clofazimine for patients with multibacillary
at increased risk of infection;8 chemoprophylaxis and disease. In 1995, a resolution was passed to provide free
BCG vaccination reduce this risk but the logistics, ethics, multidrug treatment to all leprosy patients worldwide.13
www.thelancet.com/infection Vol 11 June 2011
 Review

The World Health Assembly passed a resolution

in 1991 to “eliminate leprosy as a public health problem” A
45 Prevalence
by 2000; it defined elimination as reducing prevalence Incidence
40
to less than one case per 10 000 population.14 The effort

Number of cases per 10 000 population

accompanying this resolution included the following 35
features: the use of multidrug therapy and reclassification 30
of all cases with removal after treatment completion,
25
which is in contrast to cases being until death when
treatment was lifelong. These actions on the registers, 20
together with the widespread use of BCG vaccination, 15
which was done to protect against tuberculosis but
10
which also protects against leprosy, led to a marked
reduction in prevalence.2 Nevertheless, leprosy was not 5
eliminated and transmission continued, as use of the 0
word elimination in the resolution had led to a 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008
perception that leprosy was about to disappear, and Year
B
resulted in resources for leprosy research and control 25
being reduced.3,8,12,15 When the WHO Strategic Plan for
Leprosy Elimination was renewed, the word elimination
was replaced by the phrase “reducing leprosy burden”; 20
Number of cases per 10 000 population

this term encompasses the direct burden of disease and

the related burden of disability.1
The Millennium Development Goals were agreed at 15
the Millennium Assembly of the UN in 2000, and
committed the states of the world to a global development
project that was summarised in eight goals: eradicate 10
extreme poverty and hunger; achieve universal primary
education; promote equality for both sexes and empower
women; reduce child mortality; improve maternal health; 5

combat HIV/AIDS, malaria, and other diseases; ensure

environmental sustainability; and build a global
partnership for development.16 Leprosy is not explicitly
listed in any of the goals, but those relating to poverty,
primary education, and building a global partnership are
relevant to leprosy control. Disability is also not explicitly
included in the goals, but various ways of integrating it
have been suggested.1 In 2008, the UN Enable Convention
on the Rights of Persons with Disabilities17 was enacted,
and the UN Human Rights Council passed a resolution
on the elimination of discrimination against people
affected by leprosy and their family members.18 There
has been concern that Millennium Development Goals
might have caused an imbalance in the development
agenda, and especially that the focus on HIV/AIDS and
malaria might perpetuate the neglect of other diseases,
including leprosy.19 Leprosy is a disease of poverty. The
ensuring of equal access to diagnostic and rehabilitation
facilities and to treatment, as well as the prevention of
disability, is, therefore, important.
Epidemiology
The new case detection rate for leprosy remains high,
with about 250 000 new cases being registered each year.
Around 15 million people have been treated with
multidrug therapy, and an estimated 2 million people
have been prevented from developing disabilities.12
Although the leprosy prevalence values fell strikingly
0
1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007
Year
Figure: Incidence (new-case detection rate) and prevalence of leprosy in (A) India22 and (B) Brazil23
from 620 638 cases in 2002, to 213 036 in 2009,20,21 this
decrease is due partly to the prevalence vlaues being
halved by the duration of treatment being reduced from
24 months to 12 months. Prevalence is also affected by
operational factors, such as level of case finding activity
and integration of leprosy services into primary-health-
care services in some countries so that the leprosy
elimination targets would be reached. Data for prevalence
and incidence for India and Brazil are shown in the
figure. These data clarify the importance of using the
new case detection rate as a marker of transmission of
leprosy. High numbers of new cases continue to be
detected—249  000 were reported in 2008, of which 94%
were in the 17 countries that had reported detecting more
than 1000 new cases in that year.20,24 As shown in the
figure, the new case detection rates in Brazil continue to
be high. These data indicate ongoing transmission of
leprosy. A survey done in Maharashtra, India, showed
rates of three to nine cases per 10 000 population, and
that 30% of these newly diagnosed cases were
in children.

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 Review
A consensus has been reached by WHO that close
disease surveillance for leprosy is necessary, and four
indicators have been suggested: the number of new
cases, the new case detection rate, the treatment
completion rate (or, when feasible, cure rate), and the
rate of new cases with grade 2 disabilities.3 A new target
was introduced that the number of new cases with
grade 2 disability in 2015 should be 35% lower than
in 2010. Monitoring of the rate of new cases with disability
will pose challenges, in view of the uncertainties about
the reliability of the data. Thus, tools for accurate,
comparable grading practices are needed. Various
instruments for measuring disabilities are available,25 but
their applicability to leprosy needs to be tested. The
2009 WHO Technical Advisory Group report
recommended convening a working group to review
current practice for data collection, reporting, and
analysis to ensure that the target is valid.6
Transmission
Leprosy is caused by M leprae. Most people infected with
this organism are thought not to develop clinical disease,
although there are no tools to diagnose subclinical
infection. M leprae is slow growing and the incubation
period of leprosy is long at 2–12 years. The mode of
transmission is still not conclusively proven, although
person-to-person spread via nasal droplets is believed to
be the main route.4
Human beings are the principal reservoir of infection,
except in the Americas, where armadillos also provide a
reservoir;26 the proportion of cases attributable to
armadillos is unknown, but progress is being made in the
estimation and two-thirds of acquired cases in southern
USA have armadillo-derived strains of M leprae in the
lesions.27 Most people with leprosy are non-infectious as
the mycobacterium remains intracellular. Patients with
lepromatous leprosy, however, excrete M leprae from their
nasal mucosa and skin28 and are infectious before starting
treatment with multidrug therapy. Contacts of these
patients are, therefore, at increased risk of developing
leprosy.7 The magnitude of this risk depends on the
closeness of contact,7 with close household contacts being
at the highest risk. The risk of disease in contacts is also
related to the bacterial load of the primary case, with the
risk being twice as high in contacts of multibacillary cases
as in those of paucibacillary cases.
Whether genetic predisposition has a role in the
development of leprosy is unclear.7 Gene candidates for
susceptibility to leprosy infection have been reported, but
replication of these findings has been difficult. A genome-
wide association study of leprosy patients and healthy
controls identified new associations between variants of
genes in the NOD2-mediated signalling pathway, which
regulates the innate immune response, and determines
the risk and form of disease.7
The genome sequence of M leprae has been available
since 2001.29 Work on strain typing of M leprae has used
466
either single-nucleotide polymorphisms or short or
variable number tandem repeat genotyping. Early work
with single-nucleotide polymorphisms revealed four
subtypes of M leprae and postulated a route of spread
around the world.9 This work has been extended after
four whole-genome sequences from Brazil, India,
Thailand, and the USA were analysed, in which
201 single-nucleotide polymorphisms and 14 single-
base insertions or deletions were identified.9 This
analysis identified 16 single-nucleotide polymorphism
subtypes across 400 isolates.9 The low degree of
polymorphism arising from the four strains, for which
the genomes are 99·995% identical, suggests that there
is little variation in M leprae.
Short or variable number tandem repeat genotyping
has classified M leprae strains in several countries.11 A
potential limitation of this method is that many loci have
to be analysed to classify strains. One analysis used
genotypes from 475 M leprae strains and six different
countries, and the findings suggested that most M leprae
strains cluster together within specific countries, and
that the presence of isolates assigned to different clusters
is a consequence of migration.11 Some findings were,
however, surprising, including that the Indian strain
seems to have derived from a Philippine strain.
The short or variable number tandem repeat and single-
nucleotide polymorphism genotyping methods are best
seen as being complementary. Single-nucleotide
polymorphism analysis can be slow and the tandem
repeat method identifies many differences and is difficult
to use for epidemiological analysis apart from showing
the existence of short transmission chains in families.
Relapse is rare in leprosy, occurring in less than 1% of
patients and frequently 10 or more years after treatment.
These molecular tools are not, therefore, practical to
assess whether infection reactivation or new infection is
occurring. They could, however, be used to investigate
whether clinical outcomes, such as erythema nodosum
leprosum, are associated with different strains and
whether the M leprae strain infecting armadillos is the
same as any infecting human beings.26,27 Molecular
techniques might also clarify the mechanisms behind the
survival, persistence, and pathogenicity of M leprae.9,30–32
Clinical disease
Infection with M leprae leads to chronic granulomatous
inflammation in skin and peripheral nerves. The type of
leprosy that patients develop is determined by their cell-
mediated immune response to infection. Types may be
categorised according to the Ridley-Jopling classification,33
which is based on skin lesion type and bacterial load.
Patients with tuberculoid disease have good cell-mediated
immune response and few lesions with no detectable
mycobacteria. Patients with lepromatous leprosy are
anergic towards M leprae and have multiple lesions with
mycobacteria present. Between these two classifications
are the borderline leprosy types, in which patients have
www.thelancet.com/infection Vol 11 June 2011

some cell-mediated immune response, multiple lesions,
and unstable immunity.
WHO has introduced a simplified classification that
uses the number of skin lesions to classify disease as
paucibacillary (up to five lesions) or multibacillary (more
than five skin lesions). This classification is widely used
to guide treatment decisions. Comparison of the two
classification systems showed that in India up to 60% of
the patients with borderline tuberculoid (in the
Ridley-Jopling classification) assigned to the WHO
multibacillary group had negative slit skin smear. These
patients were, therefore, being overtreated.34 The
importance of using the more rigorous classification
in referral centres and for research studies has
been highlighted.35
Damage to nerves can occur before, during, and after
treatment and can result in disability and long-term
disfigurement, which is associated with stigma.36 A
cohort study in Ethiopia showed that 47% of 594 new
cases already had established nerve function impairment
at diagnosis and that a further 8% had recent nerve
damage. Additionally, 12% developed nerve damage after
the start of treatment, and only 33% had no clinical
evidence of nerve involvement at any time.37 The degree
of nerve damage at diagnosis reflects the delay between
the onset of symptoms and diagnosis. The delay is
frequently years, and during this time neuropathy can
develop almost unnoticed. Many nerves at diagnosis are
non-conducting and remain so.34,38,39
The inflammation present in nerves is driven by
mycobacterial antigens that activate a destructive
inflammatory immune response mediated by CD4+
cells and macrophages, and with involvement of
multiple proinflammatory cytokines, such as tumour
necrosis factor α. Markers of progression to neurological
damage have not been identified.40 A better
understanding of the immune responses behind the
nerve damage would identify high-risk patients for
closer monitoring and early intervention with existing
therapies, and guide the development of preventive and
modulating interventions.38
Type 1 and type 2 immune-mediated reactions occur in
about 30% of patients with multibacillary disease during
and after multidrug therapy.41 Steroids are the main
treatment, but a systematic review found only three trials
of adequate quality that supported this strategy.42 An
evidence-based review done by the International
Federation of Anti-Leprosy Organisations found that the
optimum duration of steroid treatment is unknown,
although some data suggest that longer courses are better,
as 20 weeks of treatment yielded better results than
12 weeks of treatment in one study.43 No studies have used
a dose-per-weight regimen. The relapse rate after steroid
therapy is 20–50%.44 Standardised tools are needed to
measure outcomes and enable comparison of study
findings. Second-line drugs for the treatment of patients
who do not respond to prednisolone are also needed.45
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Review
Erythema nodosum leprosum reactions occur in about
50% of patients with lepromatous leprosy.46 These episodes
of systemic inflammation affect skin, nerves, eyes, and
testes and are difficult to manage.47 Reactions may remit
and relapse over several years. Few studies have been done
to investigate the pathogenesis and treatment of erythema
nodosum leprosum. One review identified only three
studies published in the past 20 years.47 Current treatments
include steroids and thalidomide, but studies done with
internationally validated severity scales are needed to
identify the best treatment regimens.48 In many countries
thalidomide is not available because of fears relating to its
teratogenic potential. An international research network
to facilitate studies on pathogenesis and improved
treatments in linked centres would be beneficial.
Identification of effective treatment for post-partum
women is especially important, as they are at particularly
high risk of reactions, but are frequently under-represented
in trials.48
Owing to the similarities between tuberculosis and
leprosy, early in the HIV-1 epidemic it was feared that
HIV-1 infection would increase the risk of developing
leprosy, especially lepromatous leprosy, or that dually
infected people would have leprosy that was particularly
severe or with a poor prognosis. Although data on patients
infected with HIV and leprosy are sparse, none of these
fears has been confirmed.49 Two Brazilian studies have
shown that patients receiving highly active antiretroviral
therapy are more likely to develop borderline tuberculoid
leprosy than other types of leprosy.50,51 In HIV-1-infected
patients starting antiretroviral treatment, leprosy has
presented as immune reconstitution inflammatory
syndrome.52,53 In a review of published cases of leprosy
manifesting as this syndrome, presentations were
classified according to timing as either unmasking or as a
paradoxical clinical worsening of pre-existing leprosy:
12 (58%) were unmasking, two (9%) were paradoxical,
two (9%) were undiagnosed, and five (24%) were
unmasking followed by immune restoration.54
Treatment
WHO recommends multidrug therapy with rifampicin
and dapsone for paucibacillary disease, or with
rifampicin, dapsone, and clofazimine for patients with
multibacillary disease. The recommended duration of
therapy is 6 months for patients with paucibacillary
disease and 12 months for those with multibacillary
disease, and these regimens will effectively eradicate
M leprae in most patients. The 2009 report of the WHO
Technical Advisory Group on Leprosy Control stated
clearly that “in public health terms, it is reasonable to
conclude that infectiousness becomes unlikely after
starting multidrug therapy”.6 Longer treatment might,
however, be required in some patients with a high
bacterial index at diagnosis to prevent relapse.6 At least
one current trial is comparing different durations of
treatment for multibacillary leprosy.6
467
 Review
People with lepromatous multibacillary disease are the
main source of M leprae, and if relapse occurs in these
patients transmission resumes. This form of the disease
is, therefore, particularly important from a public health
perspective. The rate of relapse after multidrug therapy
varies, mainly owing to different follow-up methods and
definitions, but is at least below three cases per 100 person-
years, and seems to be mostly lower than two cases per
100 person-years. Factors associated with relapse include
use of monotherapy, inadequate or irregular therapy, lack
of response, presence of multiple skin lesions or thickened
nerves, and no reaction to the lepromin skin test.55
Accurate diagnosis of relapse requires clinical,
bacteriological, and therapeutic evidence; histopathology
can be helpful but frequently is not routinely available.55
The current WHO recommendation is that multidrug
therapy is restarted in cases of proven relapse.3 Relapse
and type 1 immune reaction can both lead to new skin
lesions and loss of nerve function.
Drug resistance is not yet a major issue. Patients
suspected of having resistant strains of M leprae have
responded to re-treatment with rifampicin, dapsone, and
clofazimine.3 Testing for resistance involves inoculating
mouse footpads with a patient’s tissue obtained at biopsy
and observing M leprae growth. This method is now
complemented by DNA sequencing to identify gene
mutations associated with drug resistance. Genes coding
for resistance to rifampicin, ofloxacin, and dapsone have
been identified.6 However, the clinical importance of
bacteria having a particular resistance gene remains
unknown. A worldwide surveillance initiative to assess
drug resistance in leprosy has been set up.6 The WHO
Technical Advisory Group has encouraged expanding the
work in selected countries.6 This and similar research
needs to be well supported, as no new antibiotic drugs
are in development for treating leprosy but alternative
treatment regimens are needed. Increased capacity for
drug screening, experimental chemotherapy, and clinical
trials is also required to regain treatment knowledge lost
with the success of multidrug therapy.
Diagnosis
Late diagnosis leads to continued transmission and to
increased risk of disability.15 Factors associated with late
diagnosis include delay by patients in presenting and delay
by health services in making a diagnosis. Reasons behind
patients delaying presentation vary from setting to setting,56
but stigma is likely to play a part in many cases.5 In some
countries stigma is promoted by legislation against leprosy
patients.5 Other inequalities also affect people with this
disease. Reports from Ethiopia and Bangladesh57,58 have
shown that women experience longer delays than men in
diagnosis and, therefore, frequently have a higher degree
of nerve damage and disability at diagnosis.
With decentralisation of treatment and monitoring
and decreasing numbers of cases, the maintenance of
expertise in leprosy at the peripheral level is a major
468
challenge. Richardus and Habbema59 have argued that to
eradicate an infectious disease one needs an intervention
that can interrupt transmission, practical diagnostic
tools with sufficient sensitivity and specificity to detect
all levels of infection that can lead to transmission, and
the absence of a reservoir. On the basis of these
principles, they suggest that extensive epidemiological
and microbiological research be done to identify good
tools to detect infection, and that new interventions,
such as chemoprophylaxis and vaccination, should be
developed and implemented.59
Serological tests for detection of infection and to monitor
progress under treatment have been of interest for some
time. Such tests might also be useful to identify contacts,
to monitor transmission in the community, and to guide
treatment. A range of tests are available, although none is
sufficiently specific and sensitive for leprosy. Sekar60 noted
that improvements have been made in several
immunological diagnostic tests. Developments include
assays for antibodies to PGL-1 (eg, dipstick, ELISA, ML
Flow test); new skin test antigens, such as M leprae soluble
antigens and lipoarabinomannan, wall-associated proteins
of M leprae, and their fractionates; translation of tools from
research on immunological diagnosis of tuberculosis, such
as CFP-10 and ESAT-6 proteins; and novel M leprae-specific
antigens identified after the genome sequencing of the
organism, including overlapping short peptides of different
recombinant proteins to identify specific B-cell and T-cell
epitopes.60 A more detailed review of these methods is
outside the scope of this paper.
Prevention
Chemoprophylaxis effectively lowers the incidence of
leprosy in household contacts.61 Whether to use this
approach more widely is under discussion. Single-dose
rifampicin can prevent progression of disease in people
infected with leprosy but only in non-close contacts
with low bacterial loads.61 Fears of resistance with use of
monotherapy, however, have led to the suggestion that
one or two doses of 600 mg rifampicin, 400 mg
ofloxacin, and 100 mg minocycline should be used.5
This regimen would, however, be far more expensive.
The extension of chemoprophylaxis to close non-
household contacts is supported by a good
epidemiological argument, but various practical issues
could hinder implementation of this policy. For
example, disclosure of leprosy in the index case required
for identification of contacts, especially outside the
home, might be undesirable or unethical.61 The current
recommendation in WHO’s Enhanced Global Strategy
for Further Reducing the Disease Burden due to
Leprosy10 is to examine household contacts of patients
for evidence of leprosy, if none is found to educate the
contacts on early signs of disease, and to return if these
develop. The latest report from WHO’s Technical
Advisory Group on Leprosy Control6 recommends that
a working group be formed to review the present data
www.thelancet.com/infection Vol 11 June 2011

on chemoprophylaxis and to advise on areas of research
with the aim of developing appropriate guidelines for
implementation in future leprosy control strategies.
Vaccination with BCG protects people from developing
leprosy, and neonatal BCG vaccination given to prevent
tuberculosis has probably contributed substantially to the
decrease in prevalence of leprosy. BCG is a live vaccine
and, therefore, use should be avoided in people infected
with HIV. As with tuberculosis, the degree of protection
against developing leprosy obtained from BCG varies
between populations, but the reasons for this variation
are not clearly understood.2 BCG vaccination of contacts
seems to be protective even in contacts who have already
received neonatal BCG.62,63 The timing of vaccination and
chemoprophylaxis should be considered because chemo-
prophylaxis can kill BCG.
The search for a modern, subunit protein vaccine has
been facilitated by the sequencing of M leprae, although
it is much less advanced than for tuberculosis vaccines.
The main reason for the slow progress is cost-efficiency,
as leprosy is much rarer than tuberculosis and the
incidence has been declining. Additionally, in contrast to
tuberculosis, there is no suitable animal model;
pathogenesis in mice is atypical and armadillos are not
practical for vaccine testing.64,65 If a more specific
tuberculosis vaccine is proposed to replace rather than to
boost BCG, the protection against leprosy given by
current BCG vaccination will be lost. Development of an
improved leprosy vaccine or exploration of the possibility
of adding protection against leprosy to any new
tuberculosis vaccine, therefore, also need to be urgently
explored. Findings during the development of
antituberculosis vaccines might shed some light on the
mechanism behind immunity to mycobacteria and help
the search for a new leprosy vaccine.64
Conclusions
Priorities for research in leprosy cover a wide range of
areas, from basic science to health services. Further
understanding is needed of the epidemiology, including
transmission, the role of the armadillo, and relative
contributions of transmission and reinfection to the
overall disease burden, and of the pathogenesis of nerve
damage. Effective tools must be developed for detection
of early infection, for point-of-contact diagnosis, to
predict nerve damage, and to grade disability. New
treatment regimens for leprosy and for immune-mediated
reactions need to be developed and thoroughly tested.
Finally, effective methods for monitoring drug resistance
have to be implemented. For prevention and health
services research, development of a new vaccine or
incorporation of a leprosy component into new
antituberculosis vaccines is crucial. Delivery strategies
for chemoprophylaxis of contacts need to be assessed,
and delays to diagnosis, discrimination, and stigma must
be substantially reduced. We hope that researchers and
funding will be available to take up these challenges.
www.thelancet.com/infection Vol 11 June 2011
Review
Search strategy and selection criteria
We reviewed the recommendations for research from the Leprosy International committees,
and selected a list of relevant topics. We used the term “leprosy” with each of “drug
resistance“, “nerve damage“, “detection and diagnosis of early infection“, “nerve damage“,
“vaccines“, “chemoprophylaxis“, “diagnosis/grading disability“, “new treatment regimens for
leprosy and for reactions“, “the role of armadillo, transmission“, “reactivation“, “patient and
health services delays in diagnosis“, “stigma“, and “research priorities” to search for papers
published from 2006 in PubMed, Medline, Web of Science, and Cielo. We reviewed abstracts
and full-text articles published in English, French, Italian, and Portuguese languages, and
followed up relevant citations in the reference lists of retrieved papers.
Contributors
Both authors worked equally on developing the structure for the paper,
identifying references, writing, and editing the paper.
Conflicts of interest
We declare that we have no conflicts of interest.
Acknowledgments
We thank the Special Programme for Research and Training in Tropical
Diseases, and the Disease-Specific Reference Group on Tuberculosis,
Leprosy and Buruli Ulcer for support and advice during the preparation
of this Review.
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protection: review of current evidence and status of BCG in leprosy
control. Expert Rev Vaccines 2010; 9: 209–22.
3 WHO. Enhanced global strategy for further reducing the disease
burden due to leprosy (plan period: 2011–2015). New Delhi: World
Health Organization Regional Office for South-East Asia, 2008.
4 Hatta M, van Beers SM, Madjid B, Djumadi A, de Wit MY,
Klatser PR. Distribution and persistence of Mycobacterium leprae
nasal carriage among a population in which leprosy is endemic in
Indonesia. Trans R Soc Trop Med Hyg 1995; 89: 381–85.
5 Senior K. Stigma, chemoprophylaxis, and leprosy control.
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