Memorandum on leprosy 2023

Question 1

Acknowledgments

Accepted Answer

We gratefully acknowledge all those involved in the care, diagnosis and reporting of leprosy cases in the UK.

Purpose

This document has been produced by UK Health Security Agency (UKHSA) and the Panel of Leprosy Opinion. The memorandum is based on the best available evidence and expert advice from the Panel of Leprosy Opinion.

Leprosy update: what’s new in this memorandum

The memorandum aims to be a concise but comprehensive update on the previous memorandum published in 2012. It is a didactic consensus document based on best international practice, but does not attempt to assign grades to the evidence base supporting statements made or the strength of the recommendations. The main changes since the 2012 document include:

updated current global epidemiology of leprosy
tables summarising the epidemiology of leprosy notifications in England and Wales over the past 4 decades

Authors

Panel of Leprosy Opinion

Professor Diana Lockwood (DL), Dr Steve Walker (SW), Professor Neil French, Professor Mark Bailey, Professor Nicholas Beeching, Dr Hadi Manji, Dr Ula Mahadeva, Dr Gerald Langman.

UKHSA

Dr Esther Robinson, Dr Martin Dedicoat (MD), Dr Ana Gibertoni Cruz, Dr Dona Foster (DF).

Question 2

Version control

Accepted Answer

Version	Date	Authors	Description
1.0	26 July 2022	SW, DL	Update to 2012 memorandum
1.1	10 August 2022	DF	Epidemiological update. Transfer to UKHSA template
1.2	8 December 2022	MD	Formatting
1.3	15 May 2023	Review by all panel members	Review

Question 3

Table of acronyms

Accepted Answer

Version	Date	Authors	Description
1.0	26 July 2022	SW, DL	Update to 2012 memorandum
1.1	10 August 2022	DF	Epidemiological update. Transfer to UKHSA template
1.2	8 December 2022	MD	Formatting
1.3	15 May 2023	Review by all panel members	Review

Question 4

Introduction

Accepted Answer

Leprosy is an uncommon infectious disease in England and Wales, yet it remains an important disease globally with approximately 133,802 cases notified in 2021 (1). Its importance lies in the need for early diagnosis and expert treatment and support, both for those with active disease and for those who are physically, psychologically, or socially affected by it. The objectives of this memorandum are to provide information to both clinicians and Consultants in Communicable Disease Control (CCDCs) involved in notifying and managing a person with leprosy. The memorandum draws on the best available evidence together with the specialist knowledge of the Panel of Leprosy Opinion. The full membership and a description of the remit of the panel are given in Appendix 1.

Contact details are also provided for:

consultant advisors in leprosy with experience in the diagnosis, treatment and prevention of leprosy
the Tuberculosis Surveillance Unit of UKHSA which manages notifications of leprosy and provides advice on public health action
consultant epidemiologists at UKHSA
national leprosy referral centres in England and Wales
reference laboratories performing diagnostic tests for leprosy

The memorandum aims to align with the principals of the ‘Global Leprosy Strategy: Towards Zero Leprosy 2021 to 2030 (2).

Question 5

Natural history of leprosy infection

Accepted Answer

Leprosy

Leprosy is a curable chronic infectious disease caused by the acid-fast bacillus Mycobacterium leprae (M. leprae) and more rarely mycobacterium lepromatosis. It mainly affects the cooler parts of the body such as the skin, respiratory mucosa, eyes and peripherial nerves (leprosy factsheet) (3). If detected and treated early with multidrug therapy (MDT) the disease may be cured and will not lead to disabilities.

Clinical disease has an incubation period ranging from 6 months to 20 years (4), although this may be longer (5). Most people infected with the organism are thought not to develop clinical disease but the exact proportion is not known. Once symptoms appear, the disease progresses, usually insidiously but sometimes rapidly.

Disease types

The type of disease which develops reflects the degree to which the host is able to mount a cell mediated immune response. Types of disease may be classified according to the Ridley-Jopling classification, which is based on skin lesion type and bacterial load:

Tuberculoid leprosy (TT)

Patients have a vigorous cell-mediated immune response. This results in well-demarcated lesions containing few bacilli and surrounded by lymphocytes.

Lepromatous leprosy (LL)

Patients do not develop effective cell-mediated immunity. Lesions are diffusely infiltrated with macrophages in which bacteria multiply in large numbers. Antibodies are produced, often in large quantities, but are ineffective in killing the bacilli.

Borderline leprosy (BL)

This category covers the spectrum between the 2 extremes described above. Patients have some cell-mediated immune response, multiple lesions and unstable immunity. Borderline leprosy can be further classified according to the category it most resembles:

borderline tuberculoid (BT)
borderline (mid-borderline) (BB)
borderline lepromatous (BL)

Pure neural leprosy may be any type of leprosy.

Disease description

Leprosy may be either described as paucibacillary (between one and 5 lesions) or multibacillary (6 or more lesions).

The World Health Organization

The WHO introduced a simplified field-based classification shown in Figure 1. This illustrates the different classifications and features of leprosy, and their correlation with the Bacteriological Index, which is a measure of the number of leprosy bacilli seen in stained material obtained from slit skin smears.

Figure 1. Classifications and features of leprosy

Notes

TT = tuberculoid leprosy
BT = borderline tuberculoid
BB = borderline (mid-borderline)
BL = borderline lepromatous.
LL = lepromatous leprosy
1 = calculated by counting 6 to 8 stained smears under the 100 x oil immersion lens
1+ = at least one bacillus in every 100 fields
2+ = at least one bacillus in every 10 fields
3+ = at least one bacillus in every field
4+ = at least 10 bacilli in every field
5+ = at least 100 bacilli in every field
6+ = at least 1,000 bacilli in every field

Infectivity

Leprosy is infectious when viable leprosy bacilli are shed by an untreated patient and infect a susceptible contact. The degree of infectivity depends on the concentration of leprosy bacilli in the body, and this inversely reflects the degree of the host cell-mediated immune response.

Patients with tuberculoid or borderline tuberculoid leprosy are probably not infectious. Leprosy bacilli in the tissues are extremely scanty, most are degenerate and non-viable and are intra-cellular.

In lepromatous and borderline-lepromatous leprosy, however, bacilli are numerous and present in many organs. In the lepromatous form, many millions of viable bacilli from the nasal mucosa are discharged daily from the upper respiratory tract and may remain viable for hours or days after leaving the body. Although the mode of transmission has still not been conclusively proven, droplet infection is thought to be the likeliest means of spread of the disease.

Endemic countries

In endemic countries only about 5% of household contacts of lepromatous patients develop clinical leprosy. Although chemoprophylaxis for contacts has been evaluated in and recommended in endemic countries (6), it is not undertaken or recommended in UK (7).

MDT treatment

Treatment with WHO-recommended MDT rapidly reduces the number of viable bacilli in the nasal discharge. Within a few days of starting treatment virtually all the bacilli are dead and the patient may be considered no longer infectious.

Isolation precautions

Patients with untreated leprosy do not need special isolation precautions if they require admission to health care settings. Staff do not need to wear personal protective equipment (masks and so on) for prevention of airborne infections when attending to patients in clinics or on the ward.

Type 1 and Type 2 immune-mediated reactions

Type 1 and Type 2 immune-mediated reactions can occur in almost one third of patients with multibacillary disease at presentation, during and after MDT. Leprosy reactions should be managed by a Consultant Advisor in Leprosy, and are discussed further below. The development of a reaction does not mean that the MDT treatment is failing or that the patient has become infectious. MDT should not be stopped when reactions occur.

Question 6

Global epidemiology

Accepted Answer

Global incidence

Leprosy occurs throughout the world with the highest incidence of new patients reported in the South East Asian and African regions. Table 1 shows trends in detection of new cases of leprosy by WHO region, 2010 to 2021. Brazil, India and Indonesia all reported over 10,000 cases in 2020.

Fall in global prevalence

In 2020, the prevalence of leprosy globally reported fell by 27.2% to a rate of 16.4 per million population with incidence also reduced by 37.1% to case detection rate of 16.4 per million population (1). However, the WHO state that these figures are likely a reflection of less detection and reporting during the COVID-19 pandemic (8).

New cases

Nonetheless, the global number of reported new cases has not significantly declined over the last decade (Table 1). To address this, the WHO published the Global Leprosy Strategy 2021 to 2030 (2).

Table 1. Trends in detection of new cases of leprosy by WHO region, 2009 to 2018

WHO region	2010	2011	2012	2013	2014	2015	2016	2017	2018	2019	2020	2021
Africa	25,345	19,752	22,400	20,911	18,597	21,219	20,704	20,758	20,590	20,207	16,690	21,201
Americas	37,740	36,817	36,178	33,084	33,789	28,806	27,343	29,101	30,956	29,935	19,195	19,826
Eastern Mediterranean	4,080	2,547	2,434	1,680	2,342	2,167	2,865	3,551	4,356	4,211	4,077	3,588
Europe	41	10	19	0	0	18	41	24	50	42	27	14
South-East Asia	156,254	160,132	166,445	155,385	154,834	156,118	163,095	153,487	148,495	143,787	84,818	93,485
Western Pacific	5,028	5,086	5,367	4,570	4,299	3,617	3,879	4,052	4,166	3,984	2,699	2,432
Total	228,488	224,344	232,843	215,630	213,861	211,945	217,927	210,973	208,613	202,166	127,506	140,546

Source: WHO Leprosy/Hansen’s Disease page (data accessed 10 August 2022)

Question 7

Epidemiology of leprosy in England and Wales

Accepted Answer

In 1951, leprosy became a clinically notifiable disease in England and Wales. Note that laboratories are not required to report to the Proper Authorities isolation of the causative organism of leprosy, M. leprae. At that time, a confidential register of all cases was established. Currently, a National Leprosy Surveillance Database is maintained by the Tuberculosis Surveillance Unit at UKHSA, London.

The incidence of leprosy has fallen substantially over time in the UK: 373 cases were notified between 1951 and 1960, compared to 75 between 2011 and 2020. The total number of cases notified since the inception of the register until the end of 2020 is 1,614 (Table 2).

Reflecting the global epidemiology, the majority of cases are male (1,012 of the 1,614; 72.7%) with the age range between 2 and 90 years (medium 32 years).

There have been no definite cases acquired in the UK since 1954. Prior to that, the last UK acquired case was reported in 1925. (9, 10) The most common country of birth in all decades is India, followed by Pakistan, Bangladesh, Sri Lanka and Nigeria.

However, patients had acquired infection in 34 other countries, emphasizing the need to consider the diagnosis of leprosy in migrants (9) from all continents. The country of birth recorded in the UK reflects the distribution of leprosy globally.

Under-reporting

Under-reporting is likely in the UK, as the rarity of the disease leads to low awareness of its clinical presentation and diagnosis, but the extent of this is unknown. Patients often present many years after arriving in Britain from an endemic area, so a diagnosis of leprosy may not be considered.

Table 2. New cases of leprosy in residents of England and Wales reported to the Central Register of Leprosy, 1951 to August 2022

Period	Total notifications (all types)	Number male (%)	Age at notification: range (medium)	Disease type* multi-bacillary (%)	Disease type* pauci-bacillary (%)
1951 to 1960	373	274 (73.5)	2 to 77 (30)	201 (53.9)	138 (37.0)
1961 to 1970	464	317 (68.3)	5 to 83 (30)	208 (44.8)	197 (42.5)
1971 to 1980	277	168 (60.7)	7 to 86 (33)	115 (41.5)	142 (51.3)
1981 to 1990	173	108 (62.4)	10 to 79 (34)	60 (34.7)	97 (56.1)
1991 to 2000	117	65 (55.6)	5 to 90 (37)	55 (47.0)	51 (43.6)
2001 to 2010	129	27 (20.9)*	21 to 74 (33)	21 (16.3)	11 (8.5)
2011 to 2020	75	48 (64.0)	12 to 81 (40)	36 (48.0)	29 (38.7)
2021 to August 2022	6	5 (83.3)	18 to 80 (46)	3 (50)	3 (50)
Total	1,614	1, 012 (62.7)	2 to 90 (32)	699 (43.3)	668 (41.4)

*if given.
**sex not known in 92 cases.

Source: TB Surveillance Unit, UKHSA.

Question 8

Presentation of leprosy

Accepted Answer

Diagnostic features

Box 1 summarises features in a patient which may indicate a diagnosis of leprosy. The possibility of leprosy should be borne in mind when a person has come from, or spent some time in, an endemic area (for example, India, Brazil, Indonesia, Democratic Republic of the Congo, Bangladesh, Somalia, Ethiopia, Nepal, Mozambique and Myanmar) and presents with:

a chronic, non-itchy patch in the skin which does not resemble a known condition or has not responded to treatment; a diminished cutaneous sensitivity (to light touch, pain or temperature) within an area of hypopigmentation; if there is complete anaesthesia in the skin lesion, leprosy is the leading differential diagnosis. Widespread maculation or infiltration of the skin and persistent papules or nodules which can occur in lepromatous leprosy
signs of damage to one or more peripheral nerve trunks (particularly the ulnar, median, common peroneal or posterior tibial), pain in a peripheral nerve, usually accompanied by one or more skin lesions, and/or thickened nerves or other neurological symptoms that do not fit into a well-recognised pattern
an ulcer on the sole of the foot

Leprosy may also present in spontaneous reaction, with new skin lesions, previously flat skin lesions which suddenly become erythematous or raised, neuritis, or other sudden changes in symptoms.

Less common presentations of leprosy include one or more of the following

arthritis
erythema nodosum leprosum
orchitis
acute uveitis (very rare)

Common misdiagnoses rather than a true diagnosis of leprosy include:

diabetic neuropathy
other causes of neuropathy, for example, vitamin B12 deficiency
erysipelas
Lupus vulgaris (cutaneous tuberculosis)
sarcoidosis
vasculitis
seronegative arthritis

Grade 1 disability is defined as a loss of feeling in the palm of the hand and/or the sole of the foot. Grade 2 disability is defined as visible damage to the hands such as wounds, claw hand, loss of tissue and/or visible damage to the foot such as wounds, loss of tissue or foot drop.

If the patient suspects the diagnosis there may be accompanying depression and anxiety.

Most patients are referred initially to a dermatologist, neurologist or rheumatologist.

A granulomatous skin or peripheral nerve lesion in an individual who has lived in a leprosy endemic country should be considered leprosy until proven otherwise.

Appendices 2 and 3 contain forms and notes for completing a neurological assessment.

Box 1. Leprosy: diagnosis

Patient who has resided in a leprosy endemic area (for example, India, Indonesia, Brazil, Democratic Republic of the Congo, Ethiopia, Mozambique, Bangladesh, Nepal, Sri Lanka and the Philippines).

Clinical features:

a) skin lesions:

chronic non-itchy patch with or without hypopigmentation (macular, annular or occasionally a plaque)
altered sensation (to light touch, temperature and/or pain)
widespread macules and/or infiltration with or without papules or nodules

b) peripheral nerve trunk damage and/or pain

c) thickened peripheral nerves

d) ulceration on sole of foot

e) if presenting in reaction:

acute erythema and oedema of skin lesions
sudden change in previously flat skin lesions
neuritis
other sudden change in symptoms

f) less commonly:

erythema nodosum with or without fever
hoarseness
arthritis
orchitis
acute uveitis (very rare)

Microscopy shows acid–fast bacilli (slit skin smears from skin lesions or ear lobes).

Histological findings consistent with leprosy (skin biopsy or in some cases, peripheral nerve biopsy).

Question 9

Diagnosis

Accepted Answer

Diagnosis depends on the clinical signs, the finding of acid-fast bacilli on microscopy and/or appropriate histological appearances (Box 1).

The Consultant Advisors in Leprosy will advise clinicians on any problems concerning diagnosis, potential infectivity and management of all patients with suspected leprosy and their close contacts. A consultation with the Consultant Advisors in Leprosy also gives the best opportunity for appropriate smears and/or biopsies to be taken. The diagnosis should be confirmed microscopically or histologically in every case (Box 2).

Details of microscopic examination of skin and of the recommended procedure for diagnostic skin biopsy are contained in Appendix 3. Slit skin smears (for microscopy) should only be taken by a Consultant Advisor in Leprosy or their delegate and sent to either the Hospital for Tropical Diseases in London or the Liverpool School of Tropical Medicine (Appendix 4). Finding acid-fast bacilli in such specimens confirms the diagnosis and gives an indication of the potential infectivity of the patient. Culture of specimens is not performed.

Skin biopsies

Skin biopsies should be of a depth to include some subcutaneous fat and should be immediately placed in formalin and processed for histology locally, but the specimen should be sent for review to the team of Consultant Advisors in Leprosy Histopathology at St Thomas’ Hospital in London (Appendix 4). The histopathological picture may be characteristic and pathognomonic even when bacilli cannot be demonstrated.

In rare cases where the only clinical sign is a thickened peripheral nerve with associated loss of nerve function (pure neural leprosy), the Consultant Advisor in Leprosy will advise whether a nerve biopsy is indicated.

The lepromin skin test is of no value in diagnosis. There is no serological test that provides a reliable diagnosis across the leprosy spectrum.

Nucleic acid detection tests for diagnosis of leprosy are not routinely offered in the UK. The tests available lack standardisation and have highly variable sensitivity and specificity.

PCR for M.leprae is not routinely available in the UK and is not offered as a test by the National mycobacterial reference service, either on unfixed tissue or formalin-fixed paraffin wax embedded (FFPE) tissue, as it lacks sensitivity and specificity, and is not an accredited test in the UK.

Box 2. Leprosy: the role of the clinician

Maintain an index of suspicion for leprosy.
Discuss every case with a Consultant Advisor in Leprosy before slit skin smears and/or biopsies are taken. Refer the patient to one of the national leprosy centres (Appendix 5).
Ensure any slit skin smears of skin lesions are taken by a Consultant Advisor in Leprosy or their delegate. Diagnostic skin biopsies should be taken according to the protocol in Appendix 3. Specimens for microscopy and for histological examination should be sent to reference laboratories with appropriate expertise (Appendix 4).
Notify any newly diagnosed cases of leprosy, cases with relapse, cases of leprosy new to the UK and on MDT and cases of leprosy new to the UK, diagnosed abroad and not yet on MDT (section 7.1) to the proper officer of the local authority in which the patient resides (in confidence).
Discuss the management of household contacts with the CCDC, UKHSA TB Unit, and Consultant Advisor in Leprosy if necessary (Appendix 5).

Question 10

Notification and national surveillance

Accepted Answer

Leprosy is one of 34 statutorily notifiable diseases under the Health Protection (Notification) Regulations 2010. These regulations only apply to England. Leprosy is included in the list of notifiable diseases to help ensure prompt detection and treatment, and to allow epidemiological monitoring and surveillance.

Doctors (registered medical practitioners) are required to notify any newly diagnosed cases of leprosy, cases with relapse, cases of leprosy new to the UK and on MDT or cases of leprosy new to the UK, diagnosed abroad and not on MDT, to the proper officer of the local authority in which the patient resides. Local authorities are required to notify UKHSA of such notifications.

Where the proper officer of the local authority is a UKHSA Consultant in Communicable Disease Control (CCDC) from the local Health Protection Unit (HPU), this duty is automatically effected.

Where the proper officer is a local authority employee, the local authority should notify the CCDC at the local HPU. The CCDC should then notify the Tuberculosis Surveillance Unit of:

The Travel, Acute Respiratory, Zoonoses and Emerging Infections and TB (TARZET) Division
Clinical and Public Health Group
UKHSA
61 Colindale Avenue
London NW9 5EQ

Email: TBUnit@UKHSA.gov.uk

Doctors should refer all suspected or confirmed cases to one of the national leprosy centres (Appendix 5) where the case can be reviewed by a Consultant Advisor in Leprosy.

While leprosy is not notifiable in Northern Ireland, all confirmed or suspected cases should be reported to the Public Health Agency Duty Room and managed in accordance with advice from the Consultant Leprosy Advisor.

Public Health Agency
12 to 22 Linenhall Street
Belfast BT2 8BS

Duty room telephone: 02890553997 or 02890553994

Notification of leprosy serves many purposes. It ensures that cases are managed by a Consultant Advisor in Leprosy. The CCDC will also discuss with the Consultant Advisor in Leprosy and UKHSA TB unit , the management of any close contacts, so that any necessary contact tracing is performed, with due regard to the stigma and sensitivities attached to this disease. CCDCs should keep a strictly confidential record of persons suffering from leprosy in the area covered by their HPU.

In addition, by reporting the case to the national centre, this ensures that the national surveillance system can be used to monitor the key indicators required by the WHO. These indicators include:

the number of new cases
the age and sex of the patient
the type of disease and source of acquisition

Box 3 summarises the actions for a CCDC when they are notified of a case of leprosy.

Box 3. Leprosy: the role of the CCDC

1. Ensure the patient is being managed by, or in conjunction with, a Consultant Advisor in Leprosy.

2. Ensure contact tracing is carried out and discuss the management of household contacts with the relevant Consultant at UKHSA’s Tuberculosis Surveillance Section, Colindale, and Consultant Advisor in Leprosy as appropriate.

3. Ensure the national surveillance questionnaire is completed and sent to UKHSA’s Tuberculosis Surveillance Section in order to comply with international reporting obligations and for the purposes of national surveillance.

As part of leprosy notification, each patient is allotted a unique identifier and details such as address, type of leprosy and the state of the disease are entered onto the National Leprosy Surveillance Database. After 5 years patient-identifiable data is split from clinical and socio-demographic information to be stored separately. Following this, only numbered records with clinical and socio-demographic data remain. This is consistent with the approach taken with a number of other conditions where patient identifying information is only needed for public health purposes at the time of initial reporting.

Patients on MDT who have been referred to a Consultant Advisor in Leprosy prior to January 2012 do not need to be notified. Cases newly arrived to the UK and on active MDT for leprosy and cases of leprosy new to the UK, diagnosed abroad and not on MDT, should be notified to ensure appropriate referral to a Consultant Advisor in Leprosy, and to ensure public health action is taken, if relevant.

The diagnosing clinician is responsible for notifying a case. The leprosy surveillance questionnaire may be provided by the local HPU on notifying the case. In practice, it may be agreed that the Consultant Advisor in Leprosy completes the surveillance questionnaire.

It is helpful if the type of leprosy from which the patient is suffering is indicated when the patient is first notified, even if this is only a provisional classification based on the clinical findings. The CCDC should subsequently be informed of the definitive classification as soon as further information becomes available (usually from histopathological examination). The classification used should be either the Ridley-Jopling or WHO classifications described in section 2.3.

All cases are notified confidentially. Discrimination against patients notified with the disease has not been identified in practice as a consequence of the reporting process.

There is no link between notification of a leprosy case and the exercise of powers available to local authorities or a Justice of the Peace under the Health Protection (Local Authority Powers) Regulations 2010, or the Health Protection (Part 2A Orders) Regulations 2010. Neither is notification grounds for isolation, detainment, or deportation from the UK.

Leprosy case notification does not prevent UK advocacy on the human rights and freedom of leprosy patients. The Leprosy Panel supports the aims of the UN resolution 62/215 adopted by the General Assembly in December 2010, ‘Elimination of discrimination against persons affected by leprosy and their family members’.

Question 11

Management of the patient

Accepted Answer

It is recommended that, whenever possible, patients are transferred to the care of a Consultant Advisor in Leprosy.

Management includes:

specific chemotherapy
detecting and treating recent nerve damage with corticosteroids
patient education about the disease and its treatment in order to encourage adherence and to lessen the stigma
patient education on the care of anaesthetic hands or feet
treating any immunological reactions that may arise and any sequelae from the anaesthesia
the appropriate examination of close contacts

These aspects are discussed in more detail in the following sections.

Drug therapy

The WHO now recommends one standard adult multidrug regimen: paucibacillary patients for 6 months and multibacillary patients for 12 months (11).

Antibiotic	Dose	Directly observed
Rifampicin	600mg monthly	Yes
Clofazimine	300mg monthly	Yes
Clofazimine	50mg daily	No
Dapsone	100mg daily	No

A blister pack should be used for all patients receiving WHO recommended MDT.

In the UK the type of regimen that a patient receives is determined by combining their Ridley-Jopling classification, skin smear result and biopsy findings. Paucibacillary treatment is given for 6 months to TT and BT patients with negative slit skin smears. Multibacillary treatment is given to smear positive BT, BL and LL patients for 12 months.

Clofazimine causes skin pigmentation and also increased dryness and ichthyosis of the skin of the legs and in anaesthetic areas.

Alternative drug treatments are available and should be discussed with a Consultant Advisor in Leprosy.

Improvement after starting treatment is often detectable within 7 to 14 days.

Supervision during treatment

Patients need regular supervision and encouragement both to ensure that they take the treatment as prescribed and attend for follow-up regularly, and to detect any incipient reactions, including neuritis or early damage to anaesthetic hands or feet. Patients may also need advice or help with social problems, housing and employment. A patient who has developed irreversible weakness of a hand or foot, or lagophthalmos, may require reconstructive surgery.

Length of drug treatment and follow-up

Patients with paucibacillary disease can stop treatment after 6 months treatment with the WHO regimen. Although the skin lesions may still appear active, the inflammation is due to immunological recognition of antigens from dead leprosy bacilli and not due to the activity of viable bacilli. With time, the erythema fades whether or not treatment is prolonged. Patients receiving corticosteroids for the treatment of an immunological reaction do not need to extend MDT for longer.

Immunological reactions may occur for many years after treatment. Patients must be educated about this at the time of completing chemotherapy and told to come back immediately should there be a problem. Otherwise they should be seen annually for at least 2 years after completing chemotherapy.

Patients with multibacillary leprosy should take MDT for one year.

All multibacillary patients should be reviewed at least once a year by a doctor experienced in leprosy, both during and for 5 years after completing chemotherapy. These follow-ups should include a full clinical neurological assessment and annual bacteriological examination of skin smears for the first 2 years, and subsequently as necessary. New skin and nerve lesions occurring after MDT are most likely to be reactions and should be investigated appropriately in consultation with a Consultant Advisor in Leprosy, and will usually need skin biopsy.

Dead leprosy bacilli may be detected in decreasing numbers for over 5 years in multibacillary patients after commencement of treatment, and immunological reactions may occur for at least as long.

Relapse

Relapse rates following standard MDT are very low: of the order of 1 per 100 person years, and not over 3 per 100 person years.

In paucibacillary leprosy, it is often difficult to distinguish between a late immunological reaction and an early relapse. If suspicious lesions are detected or there is evidence of deteriorating nerve function, either during or after the period of surveillance, it is recommended that the patient is urgently referred to a Consultant Advisor in Leprosy.

When any multibacillary patient who has completed treatment with standard WHO MDT shows clinical and/or bacteriological signs of relapse, it is recommended that a biopsy is performed and the patient reviewed by a Consultant Advisor in Leprosy.

Drug resistance

The WHO introduced MDT because of the rising incidence of both primary and secondary dapsone resistance. Since its introduction, no widespread clinically significant drug resistance has emerged.

Nerve damage at diagnosis

Between 30 and 60% of patients will have nerve damage at diagnosis. It is important that new nerve damage should be checked for because new nerve damage is more likely to improve with corticosteroid treatment.

Nerve damage

Nerve damage is detected by testing the motor function of the small muscles of the eyes, hands and feet and testing sensory function in the areas supplied by the ulnar, median and posterior tibial nerves. A Consultant Advisor in Leprosy should carry out this examination. Appendix 2 shows the muscles and nerves that should be tested and the sensory points to be assessed. Sensation should be tested using Semmes-Weinstein monofilaments. Nerve function should be tested every month to detect new loss.

If nerve function loss has been present for less than 6 months, a 24 week course of corticosteroids should be started.

Question 12

Complications

Accepted Answer

Reactions

Reactions are immune mediated complications of leprosy that can occur before, during or after treatment. There are 2 types of reaction:

Type 1: Erythema and oedema of skin lesions and/or acute neuritis. (Neuritis = acute loss of peripheral nerve function.)

Type 2: Erythema nodosum leprosum (ENL). Crops of tender erythematous skin lesions accompanied by systemic manifestations such as fever, malaise, neuritis, bone pain, orchitis, or iritis.

If a patient develops signs of a reaction, they should immediately contact the Consultant Advisor in Leprosy to be seen within 24 hours.

Most reactions require rapid treatment with corticosteroids to prevent nerve damage. Thalidomide may be needed to control erythema nodosum leprosum.

Nerve function should be monitored monthly during MDT to detect any new nerve damage. Patients with nerve damage at diagnosis are at highest risk of developing new nerve damage. The peak time for this is during the first 3 months of MDT.

Management of complications secondary to nerve damage

Education of patients with motor or sensory deficits helps to prevent much of the damage which results from unappreciated trauma. Patients with anaesthetic feet must wear well-fitting shoes with an appropriate microcellular rubber insole. Judicious physiotherapy helps to maintain muscle power and preserve useful function. Regular podiatry reduces the likelihood of ulceration developing in an anaesthetic foot. Patients must be asked to report immediately any new symptoms, especially pain, weakness or altered sensation, bruising or the appearance of a new ulcer.

Established deformities of hands, feet or face resulting from peripheral nerve damage may require specialised care including splints, prostheses and reconstructive surgery with suitable pre- and post-operative physiotherapy. The help of an orthopaedic surgeon skilled in reconstructive surgery in leprosy should be enlisted; the Consultant Advisor in Leprosy at the Hospital for Tropical Diseases in London will advise practitioners if necessary.

Patients suffering from lepromatous or borderline-lepromatous leprosy are at risk of developing an iridocyclitis often of insidious and painless onset. These patients should be examined regularly by an ophthalmologist.

Question 13

Admission to hospital

Accepted Answer

Out patient treatment

Most patients with newly diagnosed leprosy can be treated as out-patients without danger to themselves or others.

Hospital admissions

Hospital admission may also be indicated for medical or other reasons, including the management of immunological reactions, the care of plantar ulcers or burns or secondary infections, and for reconstructive surgery.

Any intercurrent surgical intervention, accident or other form of stress may precipitate an immunological reaction.

No special infection control precautions are required in hospital or health care settings.

Question 14

Prevention and control of leprosy in the UK

Accepted Answer

The most important measures in the control of leprosy are to identify cases as early as possible and to ensure that adequate treatment is taken for the required period of time.

Examination of contacts

Close (that is, household) contacts of all patients with leprosy should be traced and examined by a Consultant Advisor in Leprosy as they may have had a common exposure. Children are at increased risk.

The whole skin should be examined in a good light by a consultant advisor in leprosy or their delegate. Changes in the skin may appear at any time from 2 to 5 years after exposure.

BCG

Several well-designed trials show that BCG enhances any natural resistance to infection with the leprosy bacillus. For this reason, any child or young adult under 16 years who has been a household contact of a patient with leprosy should be offered BCG if they have not already had it.

Chemoprophylaxis

Chemoprophylaxis with single dose rifampicin is not recommended in the UK. It may be considered in certain circumstances for contacts of a case with multibacillary leprosy. Advice should be sought from the Consultant Advisor in Leprosy. However, this is not standard in England as there is no evidence from non-endemic settings and no transmission in the UK. There trial data is inconclusive in these settings (7, 12).

Control

Responsibility for the control of leprosy rests with the local CCDC. The CCDC should liaise with the consultant in charge of the patient, and if necessary take advice on the public health aspects of management from the Consultant Advisor in Leprosy and Consultant Epidemiologist at UKHSA, Tuberculosis Surveillance Section, Colindale. Box 3 summarises the role of the CCDC in the prevention and control of leprosy.

Health education

Misunderstandings and fear about leprosy are common in the community. The following facts about leprosy may be useful in talking to patients and their relatives:

Leprosy is a curable disease caused by an easily identifiable bacterium.

It is rare to catch leprosy from another member of the family (the last reported case in the United Kingdom was in 1954).

If leprosy is treated early and properly, disabilities can usually be prevented; treatment must be taken as prescribed and any difficulty with treatment reported to the doctor.

Leprosy is slow to develop and takes a considerable time to treat.

Leprosy affects different people in different ways. After the start of treatment, reactions to dead bacilli can occur and cause inflammation, which may need special treatment. Any new symptoms or concerns should be reported to the doctor immediately without waiting for the next planned appointment.

If loss of sensation or deformities in the skin have occurred, much can be done to prevent further damage. The patient (and his/her relatives) should be taught how to care for their skin, hands or feet to protect them and should be referred to a physiotherapist skilled in the management of paralytic deformities and anaesthetic limbs or an orthopaedic surgeon with similar skills.

Patients with leprosy can live at home, continue normal family life, work, attend hospital out-patients or be admitted to a general hospital without danger to others.

Question 15

Useful websites

Accepted Answer

World Health Organization leprosy factsheet

The International Federation of Anti-Leprosy Associations

Leprosy Information services

Leprosy Relief Association (LEPRA UK)

Question 16

References

Accepted Answer

1. ‘Global leprosy (Hansen disease) update, 2021: moving towards interruption of transmission weekly epidemiological record’ Who reference number: WER number 36, 2022: volume 97, pages 429 to 450

2. WHO. ‘Towards Zero Leprosy: Global Leprosy (Hansen’s disease) Strategy 2021 to 2030’ In: WHO, editor. New Delhi: WHO; 2021

3. WHO leprosy fact sheet

4. Lastoria JC, Abreu MA. ‘Leprosy: review of the epidemiological, clinical, and etiopathogenic aspects, part 1’ Anais Brasileiros de Dermatologia 2014: volume 89, issue 2, pages 205 to 218

5. Taggart M, Kelly A, Stell R, Chu E. ‘Multibacillary leprosy with an incubation period exceeding 50 years’ British Medical Journal Case Reports 2022: volume 15, issue 7

6. ‘Leprosy/Hansen disease: contact tracing and post-exposure prophylaxis, technical guidance’ New Delhi: WHO Regional Office for South-East Asia, 2017

7. ‘Leprosy post-exposure prophylaxis risks not adequately assessed: author’s reply’ Lancet Global Health 2021: volume 9, issue 4, pages e402 to e403

8. ‘Global leprosy (Hansen disease) update, 2020: impact of COVID-19 on global leprosy control’ WHO 2021, contract number 96

9. Lockwood DN, McIntosh A, Armstrong M, Checkley AM, Walker SL, McBride A. ‘Diagnosing and treating leprosy in a non-endemic setting in a national centre, London, 1995 to 2018’ PLoS Neglected Tropical Diseases 2022: volume 16, issue 10, page e0010799

10. Ellis CJ. ‘Leprosy in Birmingham: a review’ Postgraduate Medical Journal 1983: volume 59, issue 696, pages 652 to 654

11. Richardus JH, Mieras L, Saunderson P, Ignotti E, Virmond M, Arif MA, and others. ‘Leprosy/Hansen disease: management of reactions and prevention of disabilities, technical guidance’ New Delhi: WHO Regional Office for South-East Asia; 2017. Licence: CC BY-NC-SA 3.0 IGO

12. ‘Guidelines for the diagnosis, treatment and prevention of leprosy’ New Delhi: World Health Organization, Regional Office for South-East Asia, 2017

Question 17

Appendix 1. The Panel of Leprosy Opinion

Accepted Answer

The membership of the Panel of Leprosy Opinion is described below. The Panel of Leprosy Opinion meets once every 2 years to:

consider the local and global epidemiology of leprosy
consider changes in drug treatment, diagnostic and treatment services in the light of new research
discuss potential areas for future research
raise awareness among relevant specialties, for example, dermatology and neurology, through teaching and training

The panel reports to UKHSA via the TB Unit.

Membership of Panel of Leprosy Opinion

Dr Stephen Walker, Consultant Dermatologist, Hospital for Tropical Diseases and Department of Dermatology, University College London Hospitals NHS Foundation Trust

Professor Neil French, Consultant in Infectious Diseases, Royal Liverpool University Hospital and University of Liverpool

Professor Diana Lockwood, Emeritus Professor, London School of Tropical Medicine and Hygiene, London

Professor Mark Bailey, Consultant in Infectious Diseases, University Hospitals Birmingham NHS Foundation Trust, Birmingham.

Dr Hadi Manji, Consultant Neurologist, The National Hospital for Neurology and Neurosurgery, London.

Dr Ula Mahadeva, Consultant Histopathologist, Guys and St Thomas, NHS Trust, London

Dr Stacy Todd, Consultant Infectious diseases, Liverpool University hospitals, Foundation Trust

Question 18

Appendix 2. Notes for Completing Leprosy Neurological Assessment

Accepted Answer

Nerve palpation

Note thickening and tenderness fo the following nerves: supraorbital, cervical , greater auricular, median, ulnar, radial cutaneous, common peroneal, posterior tibial.

Nerve function

Use the MRC Grading System.

Muscle assessment

Modified 5-point MRC scale for muscle strength scoring

Hands and feet	MRC grade
Full ROM*, full resistance	5
Full ROM*, reduced resistance	4
Full ROM*, no resistance	3
Reduced ROM*, some joint movement	2
Flicker only	1
Full paralysis	0

*ROM = range of movement.

Movements and muscles tested

Nerve	Movement	Muscle or muscle group
Ulnar	Little finger abduction	Abductor digiti minimi
Ulnar	Index finger abduction	First dorsal interosseous
Median	Thumb abduction	Abductor pollicis brevis
Radial	Wrist extension	Wrist extensors
Radial	Finger extension	Finger extensors
Lateral popliteal	Foot dorsiflexion	Foot dorsiflexors
Lateral popliteal	Extension big toe	Extensor hallucis longus
Lateral popliteal	Toe fanning	Intrinsic muscles of the foot
Facial*	Raise eyebrows	Frontalis
Facial*	Closes eyes (strong and gentle closure tested)	Orbicularis oculi
Facial*	Show teeth	Obicularis oris

*In addition, eyelid gap in mm is measured and recorded.

Record reflexes. Biceps, triceps, supinator, knee, ankle.

Sensory testing

Use the nylon monofilaments on the marked sites on hands and feet.

Perform the evaluation in the sequence listed below, and document the first nylon which has a positive response.

Nylon colour	Approximate force	Interpretation
Green	(0.05gm)	Sensation within normal limits for the hand and foot
Blue	(0.2gm)	Diminished light touch sensation in the hand with difficulty in the fine tactile discrimination. Within normal limits for the foot
Purple	(2.0gm)	Diminished protective sensation in the hand but sufficient to prevent injury. Gross tactile discrimination, shape and temperature discrimination are difficult
Dark red	(4.0gm)	Loss of protective sensation for the hand, in some cases for the foot. Hands particularly vulnerable to injuries. Usually, loss of temperature discrimination
Orange	(10.0gm)	Definite loss of protective sensation for the foot. Continues to feel deep pressure and pain in both hands and feet
Bright red	(300.0gm)	Able to feel deep pressure and pain
No response	(…..)	Loss of deep pressure sensation. Usually does not feel pain. Proprioceptive sensation persists

Question 19

Appendix 3. Microscopic examination of smears and slit skin smears, and diagnostic skin biopsy for leprosy

Accepted Answer

Microscopic examination of slit skin smears:

Smears are taken from the active edge of from one to 4 skin lesions, and from the earlobes.

Slit skin smears should only be taken by a person experienced in the technique. Neuropathic ulcers of the extremities do not shed leprosy bacilli, although viable bacilli may be present in the discharges from ulcerating lesions of the proximal skin in untreated multibacillary leprosy.

Diagnostic skin biopsy

The recommended procedure for skin biopsy for leprosy diagnosis is as follows:

1. Select a representative lesion (if necessary 2 lesions) and take the biopsy from the most active part; normal skin need not be included. In tuberculoid (paucibacillary) leprosy, the biopsy should be from the active edge of the lesion.

2. The incision should be about 1.5cm x 0.5cm. Cut vertically down to the subcutaneous fat and include some fat. Alternatively, a 5mm or 6mm punch biopsy may be used.

3. Excise the specimen with care and place it in ordinary 10% formal saline (buffered or unbuffered). Record the biopsy site on the label of the bottle.

Question 20

Appendix 4. Reference laboratories for testing of specimens

Accepted Answer

Hospital for Tropical Diseases
University College London Hospital
Mortimer Market Centre
Capper Street
London
WC1E 6JB

Telephone: 0845 155 5000

Tests performed: microscopy of slit skin smears (Department of Microbiology)

Liverpool School of Tropical Medicine
Pembroke Place
Liverpool
Merseyside
L3 5QA

Telephone: 0151 705 3220

Tests performed: microscopy of slit skin smears.

Histopathology Laboratory
St Thomas’s Hospital
Lambeth Palace Road
London
SE1 7EH

Telephone : 0207 188 2934

Email: ula.mahadeva@gstt.nhs.uk

Tests performed: histopathological review (Dr Ula Mahadeva)

Question 21

Appendix 5. Contact details of consultant advisors in leprosy, national leprosy centres and consultant epidemiologists

Accepted Answer

Dr Stephen Walker

Hospital for Tropical Diseases
Mortimer Market Centre
Capper Street
London
WC1E 6JB

Telephone: 020 3447 5959

Email: uclh.htdadmin@nhs.net

Professor Neil French and Dr Stacy Todd

Tropical and Infectious Disease Unit
Royal Liverpool University Hospital
Liverpool
L7 8XP

Telephone: 0151 706 3835

Email: stacy.todd@liverpoolft.nhs.uk

Email: neil.french@liverpoolft.nhs.uk

Professor Mark Bailey

Birmingham Heartlands Hospital
University Hospitals Birmingham
Bordesley Green East
Birmingham
B9 5SS

Telephone: 0121 424 0358

Email: mark.bailey@uhb.nhs.uk

TB Unit at UKHSA

61 Colindale Avenue
Colindale
London
NW9 5EQ