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الجمعة، 3 فبراير، 2012

Guidelines for the Control of Leprosy in the Northern Territory

Guidelines for the Control of Leprosy in the Northern Territory
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Preface
Third edition considerations
Declining incidence
In 1996 the Leprosy Unit was combined with the Tuberculosis (TB) Unit in order to maximise the
efficiency of use of staff and resources in the Centre for Disease Control (CDC). Declining leprosy
detection rates allowed this to occur. We pay tribute to Dr John Hargrave and many co-workers for
40 years of dedication to the detection, treatment, and rehabilitation of persons with leprosy in the
Northern Territory (NT).
Although of continued importance, leprosy now commands an appropriately small proportion of
CDC resources, and policies involving CDC staff have been streamlined compared with the past.
Medical evidence shows that some cases are at much higher risk than others of developing nerve
function impairment (NFI) after treatment commences, or of relapsing after treatment is completed.
Similarly, some contacts are at higher risk of eventually developing disease. This knowledge allows
CDC staff to target follow-up at these groups, and discharge others to the care of primary health
services.
World Health Organization recommendations
The World Health Organization (WHO) has produced operational guidelines for leprosy control,
the
Global Strategy for Further Reducing the Leprosy Burden and Sustaining Leprosy Control
Activities (2006-2010).
and treatment techniques and the WHO leprosy classification as a purely clinical classification for
1 Changes advocated in these guidelines include simplification of diagnostic
leprosy that excludes consideration of skin smear results. Other recommendations include single
dose combination multi-drug treatment (MDT) for single lesion paucibacillary (SLPB) leprosy and
advocating for the reduction of multibacillary (MB) MDT to 12 months duration.
Technical Advisory Group Meeting on Leprosy Control in April 2006
threat of rifampicin resistant leprosy were discussed. The recommendation for the usage of single
2 At the WHO Eighth2 the implications of the potential
dose rifampicin, ofloxacin and minocycline for the treatment of SLPB leprosy
results of an Indian WHO sponsored study. This recommendation for single dose treatment for
SLPB has not been taken up in this third edition (2010) update.
The WHO 2006–2010 Global Strategy
emphasises timely detection of new cases, continued effective free chemotherapy and prevention
of disability and rehabilitation as vital factors in leprosy management.
The most recent WHO recommendations for leprosy control are outlined in the
Strategy for Further Reducing the Disease Burden due to Leprosy (Plan Period: 2011-2015)
the companion operational guidelines the
Disease Burden due to Leprosy
leprosy control in these guidelines are timely detection of new leprosy cases and prompt treatment
with MDT. Following on from this is the integration of leprosy services into the primary health care
system at a peripheral level and strengthening of referral services.
3 was based on the1 involves no new technical tools or management strategies butEnhanced Global4 andEnhanced Global Strategy for Further Reducing the(2011-2015), Operational Guidelines.5 The main principles for
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Guidelines for the Control of Leprosy in the Northern Territory
Current epidemiology
In the 5 years 2005-2009 there were 45 cases of leprosy notified in Australia.
Diseases Intelligence Annual Reports acknowledge that most of these cases are in people born
overseas from leprosy endemic countries and by 2006 there were only occasional cases from
Indigenous communities.
6 Communicable7,8
There are currently no specific national goals for leprosy disease control in Australia.
Overseas immigration to the NT
Despite the fact that the majority of recent cases have been within the Indigenous population, there
is sizeable immigration to the NT from at least 4 countries where leprosy is endemic including
refugees and other immigrants from the Democratic Republic of Congo, Myanmar, Indonesia and
India. Due to the chronic nature of leprosy, consideration of a patient’s background and assessment
and referral of any suspected cases is therefore essential.
Leprosy eradication from the NT
In the NT leprosy has been eliminated as a public health problem (defined by WHO as a prevalence
of less than 1 case per 10,000 persons). However eradication of the disease has not yet been
achieved and there is now an opportunity to move towards this at least in terms of transmission in
the Aboriginal population.
Early diagnosis
The average delay from the onset to the diagnosis of leprosy increases in settings where it is rare.
The hallmark of good leprosy control is early diagnosis that both reduces transmission to contacts
of the disease but also with multi-drug treatment that rapidly halts disease progression.
Importantly for the patient, there is also a reduced chance of NFI with early diagnosis, leading in turn
to a lower risk of new NFI during treatment, and less disability after treatment completion. These
guidelines, together with other resources and advice from the TB/Leprosy Unit, aim to facilitate
primary health personnel to opportunistically diagnose leprosy at the earliest possible point in its
presentation.
Monitoring nerve function impairment after diagnosis
Early diagnosis will reduce the percentage of patients who initially present with established NFI,
but alone it is not sufficient. NFI frequently starts or worsens after MDT treatment commences, and
sometimes after treatment completion. Nerve conduction studies are the gold standard for detecting
neuropathy, but these are not available monthly to detect recent, and thus treatable, deterioration
in nerve function. It is imperative therefore that all health workers treating leprosy have the skills to
use a simple, rapid, valid, and reliable clinical tool to detect the commonest leprosy-related NFI –
the Voluntary Muscle Test–Sensory Test (VMT-ST) (see Appendices 1 and 2).
Guidelines for the Control of Leprosy in the Northern Territory
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Part 1. Leprosy
What is leprosy?
Leprosy, also known as Hansen’s Disease, is a chronic, granulomatous infection caused by
Mycobacterium leprae,
It was discovered by the Norwegian, Gerhard A Hansen, in 1873 and principally affects the skin,
mucous membranes of the nose, and peripheral nerves.
an acid-fast bacillus (AFB) related to the bacteria causing tuberculosis.
History
Leprosy, which originates from the Latin word ‘leprosus’, meaning ‘defilement’, has been prevalent
worldwide since ancient times as a much feared and stigmatised disease. It was first introduced
into the NT towards the end of the 19
in 1882. The first recorded case in an Aboriginal person was in 1890 and there is no evidence to
th century with the first reported case in a Chinese immigrant
suggest that it existed in this population prior to this time.
Leprosy subsequently spread to involve all Aboriginal groups of the Top End of the NT, with 10%
of the population in the 1950s having clinical evidence of leprosy infection in some geographical
areas. Active case finding and treatment were combined with an integrated program of patient
education, reconstructive surgery and rehabilitation leading to a significant reduction in leprosy
cases in the NT.
Leprosy in the NT
From 1882 to the end of 2009 there have been 1484 cases of leprosy notified in the NT. Of the total,
1355 (91%) have been Aboriginal. The case detection rate for the total population has reduced
from 19 per 100,000 per year during 1970-74 to 0.6 per 100,000 per year during 2000- 2004 and
0.5 per 100,000 per year during 2005-2009 (Figure 1), a decrease of over 90%. Over the same
interval the rates for Aboriginal people have fallen from 56 per 100,000 to 2.1 per 100,000. Despite
this reduction, in the period 2000 to 2009, 7 of the 8 notified leprosy cases have been in Indigenous
people.
9
Figure 1. Mean annual leprosy case detection rates in the NT by 5-year period, 1970 - 2009
19.0
0.0
6.3
4.9
1.9 1.0 0.6 0.5
0
5
10
15
20
1970-74 1975-79 1980-84 1985-89 1990-94 1995-99 2000-04 2005-09
5 year time period
Rate per 100,000
Leprosy is now a rare diagnosis in the NT (Figure 2). Contact tracing and opportunistic diagnosis by
primary health workers has replaced community surveys as the main case-finding strategy.
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Guidelines for the Control of Leprosy in the Northern Territory
Figure 2. Notified leprosy cases in the NT since 1880 by decade of diagnosis
16 16 11 10 46 71
143
459 465
139
75
25 8
0
100
200
300
400
500
1880-
89
1890-
99
1900-
09
1910-
19
1920-
29
1930-
39
1940-
49
1950-
59
1960-
69
1970-
79
1980-
89
1990-
99
2000-
09
10 year period
Number of cases
Incidence
The WHO reports worldwide prevalence of leprosy at the beginning of 2009 as 213,036 cases. The
number of new cases detected during 2008 was 249,007, representing a global reduction of 9,126
cases (a 3.5% decrease) during 2008 compared to 2007.
10
During the past 5 years, the global number of new cases detected has continued to decrease with
the majority of countries having achieved elimination of leprosy as a public health problem (defined
as less than 1 case per 10,000 population). Leprosy continues to have pockets of high endemicity
in Angola, Brazil, the Central African Republic of the Congo, India, Madagascar, Mozambique,
Nepal, and the United Republic of Tanzania.
and numerous other countries in the Southeast Asian region.
11 Furthermore leprosy is also present in Timor-Leste10
In the NT and worldwide, access to information and early diagnosis and treatment with MDT remain
key elements in the strategy to eliminate the disease. The WHO has made MDT drugs free of
charge to all leprosy patients worldwide since 1995, providing a simple yet highly effective cure.
Mode of Transmission
Transmission of
M. leprae is primarily from untreated MB patients. The route of transmission is not
however definitely known. Evidence suggests though that the 2 main portals of entry are the skin
and the upper respiratory tract. Nasal discharge from untreated patients with active leprosy has
been shown to contain large numbers of AFB. Studies have shown experimental transmission of
leprosy via aerosols to mice and some evidence of
barrier.
M. leprae entering through breaks in the skin12
Susceptibility to infection
The overwhelming majority of people are not susceptible to leprosy and only a very small proportion
of those exposed develop the disease. A number of factors however significantly increase the risk
of developing leprosy.
These include older age persons who may reflect both weaker immune systems or the increased
likelihood of lifetime exposure, male sex, contact with a MB as opposed to PB case, genetic
closeness and increased proximity for a prolonged period to a patient for example being in the
Guidelines for the Control of Leprosy in the Northern Territory
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same household.
contacts of MB patients were shown to have a relative risk of developing leprosy 5 to 8 times that
of the general population and contacts of PB patients 2 times higher risk.
13 In a study of 8741 contacts of 1887 cases of leprosy in Malawi, the household14
M. leprae
of age. Some cases can arise in people with exposure to contacts many years previously. The
maximum incubation period is reported to be greater than 30 years in war veterans known to be
have been exposed for short periods in endemic areas but otherwise living in non-endemic areas.
The average incubation time for tuberculoid and lepromatous cases, is thought to be 2 to 5 years,
and 8 to 12 years, respectively.
Contacts who develop leprosy may only have a single skin lesion (indeterminate leprosy), which
often self-heals. Where self-healing or treatment does not occur, the disease may progress to active
leprosy (Figure 3). Those who develop the disease demonstrate an impaired cell-mediated immune
response to
in the host.
reproduces at a very slow rate and few cases are diagnosed in infants less than 1 yearM. leprae and there is evidence to suggest that there may be a genetic predisposition
Classification
In leprosy there is a continuous spectrum of disease between the 2 polar forms, tuberculoid and
lepromatous leprosy, which depends on the ability of the body to mount an immune response to
the invading bacilli. It is important to accurately classify cases by both clinical and histological
assessment, as their position on this spectrum determines infectivity, prognosis, disease
complications and treatment regimens.
Worldwide there are 2 systems used to classify leprosy patients. Proposed in 1966, the Ridley-
Jopling classification system is the most comprehensive and accurate and uses clinical and
histopathological features and the bacteriological index (BI) to identify 5 forms of leprosy. However
it is also relatively complex and therefore is now not commonly used in the field, especially in highly
endemic, low resource settings.
A second system, the WHO classification, is based on the number of skin lesions and identifies 2
forms, PB and MB. It is used as the basis of guiding MDT and was developed primarily to allow
classification and therefore rapid treatment in the field when skin smears, may not be available.
Furthermore it is easy to use and teach and allows general health workers to be confident of their
diagnosis and therefore management.
The Ridley-Jopling classification
The Ridley-Jopling classification combines clinical, histopathological, and immunological criteria to
identify 5 leprosy forms:
• Tuberculoid (TT)
• Borderline tuberculoid (BT)
• Mid-borderline (BB)
• Borderline lepromatous (BL)
• Lepromatous (LL)
In this classification, there is progression from the mildest (TT) to the disseminated form (LL) of
disease as shown in Table 1 and Figure 3.
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Guidelines for the Control of Leprosy in the Northern Territory
Table 1. Ridley-Jopling classification of leprosy
TT Polar tuberculoid
High cell mediated immunity
(Th1* immune response)
Few M. leprae
Localised disease
Smear negative
BT Borderline tuberculoid
BB Mid-borderline
BL Borderline lepromatous
LL Polar lepromatous
Low cell mediated immunity
(Th2* immune response)
Many M. leprae
Disseminated disease
Toward the TT end of the spectrum, leprosy lesions have features of a well-developed cell mediated
immunity (CMI) response or a Th1* type response and contain few AFB. Toward the LL end of the
spectrum, the immune response displays a Th2* type immune response with a poorly developed
CMI and numerous AFB.
The borderline area of the spectrum is highly unstable and represents poorly understood
Smear positive
immunoregulatory responses; BT and BB (and TT) patients are prone to disfiguring reversal
reactions (RR) while BL (and LL) patients are subject to painful erythema nodosum leprosum (ENL)
reactions (Figure 3).
*
T helper cells (Th cells) are lymphocytes that help to coordinate the immune system’s response to infection by releasing
specific types of chemicals called cytokines.
There are 2 major types of Th cell responses, Th1 and Th2.
Th1 cell cytokines produce a pro-inflammatory response and Th2 cytokines produce an anti-inflammatory response but
also promote allergic responses.
The Th1 response produces inflammation to primarily kill intracellular pathogens such as viruses and certain bacteria
like listeria and mycobacteria. They do this by activating macrophages and cytotoxic T cells, leading to ‘cell mediated
immunity’.
The Th2 response counteracts the effects of Th1 cytokines and promotes B-cells to evolve to antibody producing cells
(called plasma cells), leading to ‘humoral immunity’.
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Clinical Features of leprosy
Early lesions and indeterminate leprosy
Indeterminate leprosy represents an early form of the disease before differentiation (Figure 3) which
may present either as an area of numbness on the skin or as a visible skin lesion. The classic early
skin lesion (Figure 4) mainly occurs in children and is most commonly found on the face, extensor
surfaces of the limbs, buttocks or trunk. Scalp, axillae, groins and lumbar skin tend to be spared and
hair growth and nerve function are unimpaired.
Figure 4. Early leprosy
Source CDC collection
Infection with
Mycobacterium leprae
No disease
(majority)
Indeterminate leprosy
TT LL
BT BB BL
RR ENL
Borderline
TH1 response TH2 response
PB MB
Figure 3: The Ridley-Jopling classification of leprosy
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Guidelines for the Control of Leprosy in the Northern Territory
Skin lesions in this form tend to be either single or few in number and appear as small, flat,
hypopigmented or coppery with an irregular border. Biopsy may show the perineurovascular infiltrate
with only scanty AFB.
The majority of these cases will heal spontaneously and of the remainder, some will persist in the
indeterminate form indefinitely, but most will develop into 1 of the forms demonstrated in the Ridley-
Joping classification.
Features of established leprosy
Presentation is often with signs of nerve damage such as weakness or anaesthesia due to a
peripheral nerve lesion, or a blister, burn or ulcer in an anaesthetic hand or foot. Borderline patients
may present with reversal reactions with nerve pain, sudden palsy, multiple new skin lesions, pain
in the eye, or a systemic febrile illness.
15
Presenting symptoms
For the forms of established leprosy, clinical features are determined by the host response to
M. leprae
(TT) and lepromatous (LL) leprosy (Table 2). The clinical pattern depends on the ability of the body
to mount an immune response to the invading bacilli.
and there is a continuous spectrum of disease between the 2 polar forms; tuberculoid
Table 2. Characteristics of lesions of polar leprosy
Tuberculoid (TT) Lepromatous (LL)
Number of lesions
Very few Many to hundreds
Distribution
areas
Asymmetrical, anywhere Symmetrical, avoiding ‘spared’
Definition and clarity
hypopigmentation
Defined edge, hypopigmented Vague edge, slight
Anaesthesia
Early, marked, defined, localised
to skin lesions or major peripheral
nerve
Late, initially slight, ill-defined but
extensive, over ‘cool’ body areas
Autonomic loss
anaesthesia
Early in skin and nerve lesions Late, extensive as for
Nerve enlargement
Marked, in a few nerves Slight but widespread
Mucosal and systemic
reactions
Absent Common, severe in Type 2
Number of
M. leprae Not detectable Numerous in all affected tissues
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Tuberculoid leprosy (TT)
In the NT, TT has been the commonest form of leprosy in the past, making up more than a third of
the cases. These cases have had a well developed cell-mediated immunity and a very low bacillary
load. TT may present as purely neural, with pain or swelling of the affected nerve/s (Figure 5)
followed by anaesthesia and possible muscle weakness and wasting. Alternatively, skin lesions
may appear with or without evidence of nerve involvement. These are single or few in number and
usually present as hypopigmented (never depigmented), erythematous coppery patches, with a
well defined, but irregular, and often slightly raised border (Figure 5). The lesions are non-sweating,
have decreased hair and decreased sensation.
Diagnosis depends on clinical examination and biopsy, as smears are usually negative. Palpation
should be undertaken around the lesion for the possible palpation of a thickened nerve trunk.
Tissues other than the skin and nerves are not typically affected.
Figure 5. Characteristic nerve enlargement of tuberculoid leprosy (TT)
Source CDC collection
Figure 6. Characteristic lesion of tuberculoid leprosy (TT)
Source CDC collection
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Lepromatous leprosy (LL)
Lepromatous leprosy is less common but is a more serious and disabling disease. There is loss of
leprosy-specific mediated immunity with no check on multiplication and spread of bacilli. There is
therefore wide dissemination and a very high bacillary load.
Early symptoms include:
1. Skin lesions
are usually the first clinical manifestation as early nerve involvement is
asymptomatic. These are extensive and can be varied - macular, diffuse papules, nodular or
infiltrative. Some may resemble urticaria. There is little depigmentation, and usually no sensory
loss in the lesions. In some cases the skin can be diffusely smooth and shiny (infiltration), with
no discrete lesions.
2. Nasal symptoms
of congestion can occur resulting from infiltration of the mucous membranes
of the nose and mouth. Patients may complain of increased nasal discharge and papules and
nodules on their lips, tongue, palate or larynx. Epistaxis is common and patients can develop a
‘saddle nose deformity’ resulting from destruction of the nasal septum and cartilage.
3. Leg and ankle oedema
Subsequent to this disease progression normally occurs with numbness and anaesthesia on the
dorsal surfaces of the hands and feet and later on the extensor surfaces of the arms and legs and
due to increased capillary stasis and permeability.
finally over the trunk. There may also be infiltration of the corneal nerves that may predispose to
injury and blindness.
Left untreated the forehead and earlobes become thickened (leonine facies), and the eyebrows
become thin, particularly laterally, and are eventually lost (madarosis) (Figure 7). The nose may
collapse due to septal perforation and loss of the nasal spine and upper teeth may fall out. Skin
becomes thickened with ulcers on the hands and legs (Figure 8) and development of a glove and
stocking peripheral neuropathy. Muscle wasting can progress to deformities such as claw hand
(ulnar nerve) (Figure 9) and foot drop (common peroneal nerve).
Figure 7. Characteristic lesions of lepromatous leprosy
Source CDC collection
Other organs such as the liver, spleen, eyes (keratitis from leprous deposits) and testes (causing
atrophy) can be involved and patients may develop gynaecomastia. Renal amyloidosis is a common
complication particularly in those who develop Type 2 reactions (ENL).
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Figure 8. Characteristic anaesthetic hand and foot complications of leprosy
Source CDC collection
Figure 9. Characteristic ‘claw hand’ complication of leprosy
Source CDC collection
Borderline leprosy (BT, BB, BL)
Borderline tuberculoid (BT), mid-borderline (BB) and borderline lepromatous (BL) lie in the middle
of the polar TT to LL spectrum. This form is seen in those people with limited or variable resistance
to
structures.
Skin lesions are intermediate in number between the 2 polar forms. Asymmetrical ‘punched out’
plaques are characteristic with a distinct, raised inner edge and outer edge that merges with
surrounding skin. They may also appear as macules (erythematous or hypopigmented), nodules or
irregularly shaped bands.
Borderline disease is unstable and it can ‘upgrade’ towards TT with treatment, or ‘downgrade’
towards LL if left untreated. Neurological symptoms such as parasthesia may precede skin
changes by many years in borderline forms of leprosy with the clinical changes lagging behind the
immunological and histological changes.
M. leprae. Skin and nerve involvement is commonly seen, with only rare involvement of other
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Guidelines for the Control of Leprosy in the Northern Territory
Pure neuritic leprosy
Purely neuritic leprosy presents with asymmetrical involvement of peripheral nerve trunks with no
evident skin lesions. It may present with or without tenosynovitis and symmetric polyarthritis.
is seen more commonly in people from India or Nepal, but is not exclusive to this group. A nerve
biopsy is usually required for diagnosis and all types of leprosy may be seen on histology.
16 It
WHO classification
The WHO classification, used since 1997,
17 is based on the assessment of the number of skin
lesions and was designed to simplify and aid diagnosis of leprosy in the field and therefore guide
MDT. It allows easy assessment by health workers with only basic training, no requirement for skin
smears and is made up of 2 broad categories: paucibacillary (PB) disease (1 to 5 lesions), which
includes TT and BT, and multibacillary (MB) disease (6 or more lesions), which includes BB, BL and
LL (Table 3). PB is further divided to single lesion PB (SLPB) and PB (with 2 to 5 lesions).
Table 3. WHO classification of leprosy
18
Clinical classification
Number of skin lesions
AND AND OR
SLPB PB MBOnly 1 lesion 2 to 5 lesions 6 or more lesions
Skin smears
Negative at all sites Negative at all sites Positive at any site
Distribution
distribution
More symmetrical
distribution
- Asymmetrical
Sensation loss
Definite loss of
sensation
Definite loss of
sensation
Extensive
sensation loss
Nerve damage
(loss of sensation or
muscle weakness)
No nerve trunk
involvement Only 1 nerve trunk Many nerve trunks
Ridley-Jopling
correlation
I, TT, some BT TT, most BT Some BT, BB, BL, LL
The following flowchart (Figure 10) based on the WHO classification can also be used to aid
classification of leprosy.
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Figure 10. Classification of leprosy
Leprosy
Skin lesion with sensory loss
When skin smears are available
and dependable
When skin smears are not
available or not dependable
Single skin lesion 2 to 5 lesions More than 5 skin lesions Smear negative Smear positive
SLPB leprosy PB leprosy MB leprosy PB leprosy MB leprosy
In the NT, classification of patients is by the Ridley-Jopling classification (for prognosis) and the
WHO classification (for reporting and treatment guidance). Patients in the NT are therefore classified
for treatment on the basis of the number of skin lesions, the presence or absence of AFB on skin
smears and the histopathological findings (Table 4). Results of skin smears are an important part of
the classification process and where there is doubt about the classification based on skin lesion and
skin smears, skin histopathology may also be considered in the decision regarding final diagnosis.
In this setting where resources are available, it is important to accurately classify cases by both
clinical and histological assessment, as their position on this spectrum determines infectivity,
prognosis, disease complications and treatment regimens.
Table 4. Classification of leprosy for treatment in the NT
SLPB PB MB
Number of skin lesions
AND AND OR
1 only 2 to 5 6 or more
Skin smears (AFB)
Negative at all sites Negative at all sites Positive at any site
Histopathology (skin)
Compatible Compatible Compatible
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Guidelines for the Control of Leprosy in the Northern Territory
Diagnosis
Case definition
Definition of a leprosy case in Australia
The 2002 National Notifiable Diseases Surveillance System (NNDSS) definition for a confirmed
case of leprosy is followed in the NT. A confirmed case requires definitive laboratory criteria and 1
or more supportive clinical symptoms and signs. Only confirmed cases are reported nationally. The
NT has also added definitive laboratory critera of nucleic acid testing for
M. leprae (Table 5).
Table 5. NNDSS case definition for leprosy
A confirmed case requires either
Laboratory definitive evidence
OR
Laboratory suggestive evidence AND clinical evidence
Laboratory definitive evidence
Detection of
M. leprae by nucleic acid testing from the ear lobe or other relevant specimens.
Laboratory suggestive evidence
1. Demonstration of acid fast bacilli in slit skin smears or biopsies prepared from the ear lobe or
other relevant sites; OR
2. Histopathological report from skin or nerve biopsy compatible with leprosy (Hansen’s disease)
examined by an anatomical pathologist or specialist microbiologist experienced in leprosy
diagnosis.
Clinical evidence
3. Compatible nerve conduction studies; OR
4. Peripheral nerve enlargement; OR
5. Loss of neurological function not attributable to trauma or other disease process; OR
6. Hypopigmented or reddish skin lesions with definite loss of sensation.
A different working definition is used when reporting Australian leprosy cases to the WHO. This is
based on the
3 ‘cardinal signs of leprosy’(see box below). In this context, a case of leprosy is
defined as “a person showing 1 or more of the following features, and who has yet to complete a
full course of treatment”.
Cardinal signs of leprosy
1. Hypo-pigmented or reddish localised skin lesions with definite loss of sensation (particularly
of touch and temperature); OR
2. involvement of the peripheral nerves, as demonstrated by definite thickening with loss of
sensation (particularly of touch and temperature); OR
3. skin smear positive for AFB.
Clinical Assessment
A complete history and physical examination in addition to laboratory tests are essential to diagnosis
of leprosy. The main components of the clinical assessment are:
1. History
2. Skin examination
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3. Nerve palpation
4. Nerve function impairment (NFI) assessment – voluntary motor test-sensory test (VMT-ST)
5. Eye examination
6. Deformity, disability and psychological assessment
Use the leprosy examination forms for skin (Appendix 3) at the time of diagnosis and annually, and
for nerves, NFI, and eyes (Appendix 2) monthly while on treatment and at routine follow-up after
treatment.
History
While history taking, enquire specifically about the presence and duration of lesions, nerve pain,
numbness and tingling, weakness, ulcers and injuries, eye pain and worsening vision. It is also
important to determine any underlying disability resulting from their illness on initial consultation. In
addition, assess possible previous exposure to leprosy and current contacts.
Skin examination
The entire skin surface should be examined carefully for lesions that can include macules, papules,
plaques, nodules, urticaria-like lesions and smooth infiltrations. Patches may appear coppery on
dark skin and pink on fair skin. Sometimes the only lesions are on the buttocks. Look for loss of
sensation, hair, pigmentation and sweating. Natural sunlight is the best light for detecting subtle
changes, but ensure privacy and patient comfort.
Same-sex examiners or the presence of a friend may be required. Since loss of sensation in a patch
is a cardinal sign, demonstration of this sign must be done systematically to accurately determine its
presence (Table 6). Digital photography of skin lesions at the time of diagnosis and on completion
of treatment is recommended. Consent should be obtained from the patient.
Table 6. Method of testing loss of sensation in a patch
Environment
Privacy, relaxed patient, 1 examiner.
Cotton wool
Roll it to a point, touch the skin so the point bends, don’t stroke it.
Explain
“I’m going to do this…” and demonstrate touch on your own arm.
Trial test
With patient’s eyes open, touch an area of normal skin with cotton wool. Ask
them to point to the spot where they felt the touch with their index finger.
Real test
ask patient to touch each time the spot where they feel the wool.
With patient’s eyes closed, test normal skin near the patch, then the patch -
Interpretation
Loss of sensation if no response.
(misreference).
Reduced sensation if they touch >3cm away from the point you touch
Normal sensation if localised within 3cm.
Errors
Areas of thick skin which are normal may not feel cotton wool (soles, elbows).
Leprosy patch may not be insensitive on the face.
Children
Cooperation may be difficult – look for loss of sweating in the patch instead -
ask the child to run around in the sun, then examine.
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Guidelines for the Control of Leprosy in the Northern Territory
Nerve palpation
The most commonly affected nerves are: ulnar, median, radial cutaneous, common peroneal
(lateral popliteal) and posterior tibial nerves, the sural nerve, the 5
greater auricular nerve. Widespread involvement of cutaneous nerves is also common. Patients
may present with limb deformities and chronic ulceration and scarring on hands and feet as a
result of trauma to areas with loss of sensation. Patients may also present with neuropathic joints,
traumatised by repeated injury to a joint with no protective sensation.
th and 7th cranial nerves, and the
The nerves are affected by leprosy at the most superficial, and thus coolest points in their course,
since
easily felt. Learn the size of normal nerves by practising palpation on yourself and friends (Table 7).
Examine the nerve on both sides simultaneously to help differentiate whether 1 is abnormal. Use 3
M. leprae prefers to multiply in vivo at a temperature of 27-30° Celsius. Therefore they are
fingers to roll the nerve
gently against the bone - nerves may be very tender if inflamed.
Table 7. Method of palpation of commonly involved nerves
Supraorbital
nerve may be felt 1cm from the inner end of the eyebrow if enlarged.
Run examiner’s thumb-tips just above both eyebrows of the patient – the
Greater
auricular
Turn the head to 1 side and feel along the opposite sternomastoid muscle.
Ulnar
With patient’s arms flexed to 90° feel in the bony groove just inside (medial
to) the point of the elbow, and follow the nerve up for 10cm.
Median
large tendon (medial to the flexor carpi radialis tendon).
Feel at the wrist crease next to the palm just on the small finger side of a
Radial
cutaneous
Roll it over the lateral side of the radius near the wrist crease.
Common
peroneal
With the patient seated, find the fibular head - 2cm down (distally) and
1cm behind it (posteriorly) the nerve is felt winding around the neck of the
fibula.
Posterior tibial
(medial malleolus).
Palpate 2cm down and 2cm behind the point of the inner ankle bone
Nerve function assessment (VMT-ST)
This is discussed in Part 2, p 36 and in Appendix 1.
Eye examination
Gerhard Armauer Hansen, who discovered the leprosy bacillus, claimed in 1873, “there is no
disease which so frequently gives rise to disorders of the eye, as leprosy does”.
not this remains true today, it underscores the importance of examining for the common ocular
manifestations of leprosy in a suspected case (Table 8).
19 Whether or
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Table 8. Common ocular manifestations of leprosy
Complication Description Mechanism Class Signs/Symptoms
Madarosis
and lashes
Loss of eyebrows
Bacillary infiltration/
destruction of follicles
MB Observe loss
Corneal
hypoaesthesia
Reduced corneal
sensation to
cotton wool (not
anaesthesia)
Trigeminal nerve –
damage to the small
branches innervating
cornea
Borderline Observe spontaneous
blinking. Test with cotton
wool wisp if less than 3
blinks per minute*
Lagophthalmos
paralysis of the
orbicularis oculi
muscles leading to
lid gap
Facial nerve –
damage to the
zygomatic branch
with Type 1 reaction
in a skin patch
overlying the
cheekbone
Borderline Gentle eye closure
Eye closure with effort,
and against resistance
Exposure keratitis
(lower half of cornea dry,
scarred)*
Weakness or
Iridocyclitis
Inflammation of
the iris and ciliary
body
Type 2 reaction MB Eye pain/ache
Photophobia
Tenderness
Tearing
Redness (perilimbal)
Small, poorly reactive,
ovoid pupil
Dull cornea
Reduced visual acuity
Scleritis
Inflammation of
the sclera near the
cornea
Type 2 reaction MB Eye pain and
tenderness
Deep red scleral patch
Dacrocystitis
lacrimal sac
Infection of the
Bacillary infiltration in
the nasal mucosa (or
nasal collapse) blocks
the nasolacrimal duct,
causing stagnation
and infection
MB Tearing
Pus expressed from
punctum in lower lid
Swelling and tenderness
over lacrimal sac
(between eye and nose)
Ectropion
out lower lid
Sagging turned
Bacillary infiltration
and distortion of lid
MB Tearing
Exposure keratitis
Entropion
towards eyeball
Lid turned in
Bacillary infiltration
and distortion of lid
MB Tearing
Conjunctivitis
Scarred cornea from
turned in lashes
(trichiasis)
Cataract
(commonest),
secondary to chronic
iridocyclitis or steroid
treatment of NFI
All Reduced visual acuity
Milky opacity in pupil
Lens opacity Primary age-related
Opacity in red reflex
* See Appendix 1
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Guidelines for the Control of Leprosy in the Northern Territory
Deformity, disability and psychological assessment
An assessment of deformity or disability is an important part of the initial clinical assessment.
Deformities can result from infection, relapse or Type 1 and Type 2 immune reactions and all can
lead to irreversible nerve damage. This in turn can impact upon the patient’s psychological and social
wellbeing, leading to anxiety or depression that is compounded by the stigmatised view of leprosy
in many societies. Signs and symptoms of these disorders should therefore be sought during the
history and examination and appropriate referrals made to provide support to the patient.
Investigations
The diagnosis of leprosy is based primarily on demonstrated clinical features and can be confirmed
by skin smears, skin biopsy or nerve biopsy.
Slit skin smears
A slit skin smear may demonstrate the presence of AFB in the skin. AFB are always present in the
LL or BL cases, but will not be found in the TT or indeterminate forms.
Indications
1. For diagnosis where there is clinical suspicion of disease.
2. To monitor treatment in lepromatous (MB) cases.
3. Suspicion of relapse after completion of MDT.
Preferred sites
1. Both ear lobes.
2. Suspicious skin patches – 2 smears taken from the edge if the lesion is distinct, and from the
centre if the lesion is indistinct.
3. Thickened skin on forehead above the medial border of the eyebrows.
4. Knees or elbows.
5. Previously positive sites.
(
Sites 1 and 2 are minimum requirements)
Procedure
1. Wash microscope slide in water and dry with methylated spirits.
2. Clean earlobe with alcohol swab and let it dry.
3. Optionally, apply EMLA cream to all sites and allow 30 minutes to anaesthetise the skin.
4. When desired effect achieved (test with sterile needle prick), wipe EMLA from skin (wearing
gloves will prevent the examiner’s finger tips from becoming numb).
5. Squeeze sample area or roll between index finger and thumb until it becomes bloodless (white).
This requires a lot of pressure - initially using 2 hands to squeeze is helpful.
6. Make an incision about 5mm long and 3mm deep with a size 15 Bard Parker scalpel blade.
7. Turn the blade at right angles to the cut and without relaxing finger pressure scrape the incision
with the slanted edge of the scalpel blade several times in 1 direction.
8. Tissue obtained should be gently smeared on a small area of the slide in a central circle.
Samples with obvious blood content are unlikely to be useful so wiping the sample site with a
cotton swab while maintaining pressure may enable you to collect a second sample, that is not
bloody, without a repeated incision.
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9. Fix the slide by passing the
underside for 2 seconds over a naked flame (a lit match, cigarette
lighter, or spirit lamp) until the slide feels slightly warm on the back of your hand.
10. Label slide with site of smear, and patient details, and place in cardboard holder.
11. Send to Royal Darwin Hospital Microbiology Laboratory requesting AFB for leprosy.
12. A smear from different sites in the same patient is useful for diagnosis.
Nasal mucous membrane smears can also be taken, using a sterile cotton wool bud, and wiping
firmly in the nasal passage. The smear is then prepared in the same way as for skin smears as
outlined above from points 8 to 11.
Laboratory reporting of skin smears
The Bacterial Index (BI) (Table 9) is a mean score that quantifies bacilli in the skin. It is derived by
adding the scores from each site and dividing by the number of sites sampled. The grades range
from 0+ to 6+, depending on the number of bacilli seen in an average microscopic field using an oil
immersion lens or high power field (hpf). In untreated lepromatous leprosy the BI is 5+ or 6+. It falls
with treatment by approximately 0.75 –1.0+ BI units per year, and can therefore be used to gauge
response to treatment for MB leprosy, as well as for initial classification or detecting relapse.
Table 9. Bacterial index definitions for skin smears
Bacterial index Description
0+
0 bacilli in 100 hpf
1+
1-10 bacilli in 100 hpf
2+
1-10 bacilli in 10 hpf
3+
1-10 bacilli in 1 hpf
4+
10-100 bacilli in 1 hpf
5+
100-1000 bacilli in 1 hpf
6+
The morphological index (MI) is the percentage of solidly stained bacilli of normal size and shape.
These bacilli are thought to be the viable, living bacteria that could potentially infect others.
AFB in skin smears may also be reported as ‘fragmented’ meaning recently dead, or ‘granular’
suggesting old, non-viable bacteria. These descriptions are used in the SFG (Solid-Fragment-
Granule) reading reported by the laboratory.
The MI falls rapidly to zero after MDT is commenced indicating a bactericidal effect, whilst a high BI
can take years to reach zero since it relies on the gradual clearance of debris. The MI is often not
used in routine practice due to problems with standardisation and reproducibility.
>1000 bacilli in 1 hpf
Skin or nerve biopsy
Biopsy of affected nerve or skin is sometimes necessary in cases where the diagnosis may be
uncertain. When a skin biopsy is performed the incision should contain the whole depth of the
dermal layer so that AFB in the deeper layers of the dermis will not be missed. They should also be
taken from areas of skin with the most active disease.
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Guidelines for the Control of Leprosy in the Northern Territory
Method for skin biopsy
1. Clean the site and inject local anaesthetic deep into the subcutaneous tissue around the biopsy
site. Do not inject intradermally as it ruins the biopsy.
2. Insert a cotton tie into the end of the site and use this as a retractor (forceps crush the
tissues).
3. Excise an elliptical piece of skin approximately 1 centimetre long and down to subcutaneous
fat (about 5mm deep) such that the dermis is included (leprous changes may occur in the deep
layers of the dermis).
4. Place most of the biopsy tissue into Buffered Formal Saline (10% formalin) and request
histopathology with Wade-Fite stain for AFB, and fungal stains. Save a small piece of biopsy
as a fresh specimen and request fungal culture.
5. Send all samples to Royal Darwin Hospital Microbiology Laboratory.
A nerve biopsy may be indicated where a skin biopsy has not been diagnostic or in cases of purely
neuritic leprosy. In this case a thickened area of nerve should be sampled ie. radial cutaneous
nerve at the wrist, or at the ankle the superficial peroneal, sural or posterior tibial nerve (this is the
most commonly affected nerve in leprosy). A surgical consultation to obtain this is required.
PCR based assays
There have been several polymerase chain reaction (PCR) methods developed for detecting
M. leprae
also relatively expensive, impractical for field use and while not widely available are becoming
DNA in biopsies. These methods are potentially both sensitive and specific, but are
increasingly utilised in Australian laboratories.
Differential diagnosis
The differential diagnosis of leprosy is broad. The consideration of leprosy when skin and nerve
pathology is suggested is key to diagnosis and adherence to the clinical criteria for diagnosis
will facilitate a correct diagnosis. The following should be considered in differential diagnosis of
leprosy.
20
Commonly occurring conditions
1. Birth marks (naevus anaemicus)
are well-defined hypopigmented skin patches that are present
from birth and are typically single or few in number. Sweating and sensation is normal.
2. Vitiligo
damage. Sensation, sweating and skin texture are normal.
lesions are white lesions with white hairs caused by depigmentation due to melanocyte
3. Post-inflammatory hypochromia
is a reduction of normal pigment at the site of previous
inflammation from wounds or simple inflammatory conditions and may mimic early leprosy.
4. Scar tissue
due to skin injury may show sensation loss and resemble a patch of PB leprosy.
5. Litchenoid dermatitis
and sensation. Sometimes lesions may looks like coins ‘nummular-like dermatoses’.
presents with scaly, itchy hypopigmented lesions with normal sweating
6. Tinea versicolor
furfur
is a fungal infection often co-existing with leprosy and caused by Malasseziawith well-defined, scaly brown lesions on the trunk, neck and limbs. Diagnosis is based
on assessment under Wood’s lamp and identifying fungus in skin scrapings.
7. Tinea corporis
often presents with well defined, round lesions, with a raised and vesicular
edge. There may be 2 or more concentric rings and the lesions are usually scaly and itchy

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