Wim H. van Brakel

Measuring health-related stigma—A literature review

Stigma related to chronic health conditions such as HIV/AIDS, leprosy, tuberculosis, mental illness and epilepsy is a global phenomenon with a severe impact on individuals and their families, and on the effectiveness of public health programmes. To compare stigma measurement in different disciplines, a literature review was conducted. References were obtained through a search of literature databases and through examining relevant bibliographies. Sixty-three papers were selected that addressed the issue of measurement of stigma or related constructs and that contained a sample of the instrument or items used. Five unpublished studies were also included in the review. The aspects of health-related stigma used for assessment can be grouped in five categories. First, the experience of actual discrimination and/or participation restrictions on the part of the person affected; second, attitudes towards the people affected; third, perceived or felt stigma; fourth, self or internalized stigma; and fifth, discriminatory and stigmatizing practices in (health) services, legislation, media and educational materials. Within each of these areas, different research methods have been used, including questionnaires, qualitative methods, indicators and scales. The characteristics of the instruments considered most promising are described and compared. The purpose of stigma assessment is to increase our understanding of stigma and its determinants and dynamics, to determine its extent or severity in a given setting or target group and to monitor changes in stigma over time. The conclusions from this review are that (a) the consequences of stigma are remarkably similar in different health conditions, cultures and public health programmes; (b) many instruments have been developed to assess the intensity and qualities of stigma, but often these have been condition-specific; and (c) development of generic instruments to assess health-related stigma may be possible. To achieve this aim, existing instruments should be further validated, developed or adapted for generic use, where possible.Abstract Stigma related to chronic health conditions such as HIV/AIDS, leprosy, tuberculosis, mental illness and epilepsy is a global phenomenon with a severe impact on individuals and their families, and on the effectiveness of public health programmes. To compare stigma measurement in different disciplines, a literature review was conducted. References were obtained through a search of literature databases and through examining relevant bibliographies. Sixty-three papers were selected that addressed the issue of measurement of stigma or related constructs and that contained a sample of the instrument or items used. Five unpublished studies were also included in the review. The aspects of health-related stigma used for assessment can be grouped in five categories. First, the experience of actual discrimination and/or participation restrictions on the part of the person affected; second, attitudes towards the people affected; third, perceived or felt stigma; fourth, self or internalized stigma; and fifth, discriminatory and stigmatizing practices in (health) services, legislation, media and educational materials. Within each of these areas, different research methods have been used, including questionnaires, qualitative methods, indicators and scales. The characteristics of the instruments considered most promising are described and compared. The purpose of stigma assessment is to increase our understanding of stigma and its determinants and dynamics, to determine its extent or severity in a given setting or target group and to monitor changes in stigma over time. The conclusions from this review are that (a) the consequences of stigma are remarkably similar in different health conditions, cultures and public health programmes; (b) many instruments have been developed to assess the intensity and qualities of stigma, but often these have been condition-specific; and (c) development of generic instruments to assess health-related stigma may be possible. To achieve this aim, existing instruments should be further validated, developed or adapted for generic use, where possible.

The Participation Scale: measuring a key concept in public health.

Purpose. To develop a scale to measure (social) participation for use in rehabilitation, stigma reduction and social integration programmes. Method. A scale development study was carried out in Nepal, India and Brazil using standard methods. The instrument was to be based on the Participation domains of the International Classification of Functioning, Disability and Health (ICF), be cross-cultural in nature and assess client-perceived participation. Respondents rated their participation in comparison with a ‘peer’, defined as ‘someone similar to the respondent in all respects except for the disease or disability’. Results. An 18-item instrument was developed in seven languages. Crohnbachs α was 0.92, intra-tester stability 0.83 and inter-tester reliability 0.80. Discrimination between controls and clients was good at a Participation Score threshold of 12. Responsiveness after a ‘life change’ was according to expectation. Conclusions. The Participation Scale is reliable and valid to measure client-perceived participation in people affected by leprosy or disability. It is expected to be valid in other (stigmatised) conditions also, but this needs confirmation. The scale allows collection of participation data and impact assessment of interventions to improve social participation. Such data may be compared between clients, interventions and programmes. The scale is suitable for use in institutions, but also at the peripheral level.

Disability in people affected by leprosy: the role of impairment, activity, social participation, stigma and discrimination

Background : Leprosy-related disability is a challenge to public health, and social and rehabilitation services in endemic countries. Disability is more than a mere physical dysfunction, and includes activity limitations, stigma, discrimination, and social participation restrictions. We assessed the extent of disability and its determinants among persons with leprosy-related disabilities after release from multi drug treatment. Methods : We conducted a survey on disability among persons affected by leprosy in Indonesia, using a Rapid Disability Appraisal toolkit based on the International Classification of Functioning, Disability and Health. The toolkit included the Screening of Activity Limitation and Safety Awareness (SALSA) scale, Participation Scale, Jacoby Stigma Scale (anticipated stigma), Explanatory Model Interview Catalogue (EMIC) stigma scale and Discrimination assessment. Community members were interviewed using a community version of the stigma scale. Multivariate linear regression was done to identify factors associated with social participation. Results : Overall 1,358 persons with leprosy-related disability (PLD) and 931 community members were included. Seventy-seven percent of PLD had physical impairments. Impairment status deteriorated significantly after release from treatment (from 59% to 77%). Around 60% of people reported activity limitations and participation restrictions and 36% anticipated stigma. As for participation restrictions and stigma, shame, problems related to marriage and difficulties in employment were the most frequently reported problems. Major determinants of participation were severity of impairment and level of education, activity and stigma. Reported severity of community stigma correlated with severity of participation restrictions in the same districts. Discussion : The majority of respondents reported problems in all components of disability. The reported physical impairment after release from treatment justifies ongoing monitoring to facilitate early prevention. Stigma was a major determinant of social participation, and therefore disability. Stigma reduction activities and socio-economic rehabilitation are urgently needed in addition to strategies to reduce the development of further physical impairment after release from treatment.

Early Diagnosis of Neuropathy in Leprosy—Comparing Diagnostic Tests in a Large Prospective Study (the INFIR Cohort Study)

Background Leprosy is the most frequent treatable neuromuscular disease. Yet, every year, thousands of patients develop permanent peripheral nerve damage as a result of leprosy. Since early detection and treatment of neuropathy in leprosy has strong preventive potential, we conducted a cohort study to determine which test detects this neuropathy earliest. Methods and Findings One hundred and eighty-eight multibacillary (MB) leprosy patients were selected from a cohort of 303 and followed for 2 years after diagnosis. Nerve function was evaluated at each visit using nerve conduction (NC), quantitative thermal sensory testing and vibrometry, dynamometry, monofilament testing (MFT), and voluntary muscle testing (VMT). Study outcomes were sensory and motor impairment detected by MFT or VMT. Seventy-four of 188 patients (39%) had a reaction, neuritis, or new nerve function impairment (NFI) event during a 2-year follow-up. Sub-clinical neuropathy was extensive (20%–50%), even in patients who did not develop an outcome event. Sensory nerve action potential (SNAP) amplitudes, compound motor action potential (CMAP) velocities, and warm detection thresholds (WDT) were most frequently affected, with SNAP impairment frequencies ranging from 30% (median) to 69% (sural). Velocity was impaired in up to 43% of motor nerves. WDTs were more frequently affected than cold detection thresholds (29% versus 13%, ulnar nerve). Impairment of SNC and warm perception often preceded deterioration in MF or VMT scores by 12 weeks or more. Conclusions A large proportion of leprosy patients have subclinical neuropathy that was not evident when only MFT and VMT were used. SNC was the most frequently and earliest affected test, closely followed by WDT. They are promising tests for improving early detection of neuropathy, as they often became abnormal 12 weeks or more before an abnormal monofilament test. Changes in MFT and VMT score mirrored changes in neurophysiology, confirming their validity as screening tests.

Steroid prophylaxis for prevention of nerve function impairment in leprosy: randomised placebo controlled trial (TRIPOD 1).

Abstract Objective To determine whether addition of low dose prednisolone to multidrug treatment can prevent reaction and nerve function impairment in leprosy. Design Multicentre, double blind, randomised, placebo controlled, parallel group trial. Setting Six centres in Bangladesh and Nepal. Participants 636 people with newly diagnosed multibacillary leprosy. Intervention Prednisolone 20 mg/day for three months, with tapering dose in month 4, plus multidrug treatment, compared with multidrug treatment alone. Main outcome measures Signs of reaction, impairment of sensory and motor nerve function, and nerve tenderness needing full dose prednisolone at four months and one year. Results Prednisolone had a significant effect in the prevention of reaction and nerve function impairment at four months (relative risk 3.9, 95% confidence interval 2.1 to 7.3), but this was not maintained at one year (relative risk 1.3, 0.9 to 1.8). Fewer events occurred in the prednisolone group at all time points up to 12 months, but the difference at 12 months was small. Subgroup analysis showed a difference in response between people with and without impairment of nerve function at diagnosis. Conclusions The use of low dose prophylactic prednisolone during the first four months of multidrug treatment for leprosy reduces the incidence of new reactions and nerve function impairment in the short term, but the effect is not sustained at one year. The presence of nerve function impairment at diagnosis may influence the response to low dose prednisolone.

Cytokine and Protein Markers of Leprosy Reactions in Skin and Nerves: Baseline Results for the North Indian INFIR Cohort

Background Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for reaction and nerve damage. This study characterised the cellular infiltrate in skin and nerve biopsies using light microscopic and immunohistochemical techniques to identify any association of cytokine markers, nerve and cell markers with leprosy reactions. Methodology/Principal Findings TNF-α, TGF-β and iNOS protein in skin and nerve biopsies were detected using monoclonal antibody detection immunohistochemistry techniques in 299 skin biopsies and 68 nerve biopsies taken from patients at recruitment. The tissues were stained with hematoxylin and eosin, modified Fite Faraco, CD68 macrophage cell marker and S100. Conclusions/Significance Histological analysis of the biopsies showed that 43% had borderline tuberculoid (BT) leprosy, 27% borderline lepromatous leprosy, 9% lepromatous leprosy, 13% indeterminate leprosy types and 7% had no inflammation. Forty-six percent had histological evidence of a Type 1 Reaction (T1R) and 10% of Erythema Nodosum Leprosum. TNF-α was detected in 78% of skin biopsies (181/232), iNOS in 78% and TGF-β in 94%. All three molecules were detected at higher levels in patients with BT leprosy. TNF-α was localised within macrophages and epithelioid cells in the granuloma, in the epidermis and in dermal nerves in a few cases. TNF-α, iNOS and TGF-β were all significantly associated with T1R (p<0.001). Sixty-eight nerve biopsies were analysed. CD68, TNF-α and iNOS staining were detectable in 88%, 38% and 28% of the biopsies respectively. The three cytokines TNF-α, iNOS and TGF-β detected by immunohistochemistry showed a significant association with the presence of skin reaction. This study is the first to demonstrate an association of iNOS and TGF-β with T1R.

Measuring leprosy-related stigma - a pilot study to validate a toolkit of instruments

Purpose. Stigma negatively affects the quality of life of leprosy-affected people. Instruments are needed to assess levels of stigma and to monitor and evaluate stigma reduction interventions. We conducted a validation study of such instruments in Tamil Nadu and West Bengal, India. Methods. Four instruments were tested in a ‘Community Based Rehabilitation’ (CBR) setting, the Participation Scale, Internalised Scale of Mental Illness (ISMI) adapted for leprosy-affected persons, Explanatory Model Interview Catalogue (EMIC) for leprosy-affected and non-affected persons and the General Self-Efficacy (GSE) Scale. We evaluated the following components of validity, construct validity, internal consistency, test–retest reproducibility and reliability to distinguish between groups. Construct validity was tested by correlating instrument scores and by triangulating quantitative and qualitative findings. Reliability was evaluated by comparing levels of stigma among people affected by leprosy and community controls, and among affected people living in CBR project areas and those in non-CBR areas. Results. For the Participation, ISMI and EMIC scores significant differences were observed between those affected by leprosy and those not affected (p = 0.0001), and between affected persons in the CBR and Control group (p < 0.05). The internal consistency of the instruments measured with Cronbachs α ranged from 0.83 to 0.96 and was very good for all instruments. Test–retest reproducibility coefficients were 0.80 for the Participation score, 0.70 for the EMIC score, 0.62 for the ISMI score and 0.50 for the GSE score. Conclusion. The construct validity of all instruments was confirmed. The Participation and EMIC Scales met all validity criteria, but test–retest reproducibility of the ISMI and GSE Scales needs further evaluation with a shorter test–retest interval and longer training and additional adaptations for the latter.

The Missing Millions: A Threat to the Elimination of Leprosy

Leprosy is a slow, chronic disease with a long incubation period caused by Mycobacterium leprae. The clinical presentation varies across a wide spectrum from tuberculoid to lepromatous leprosy. The condition is characterized by skin lesions and damage to peripheral nerves leading to physical disability and social problems. The past 50–60 years have witnessed remarkable progress in the fight against leprosy. The introduction of dapsone therapy in the late 1940s was the first effective treatment for leprosy, and this was followed by the move to short course multidrug therapy (MDT) in 1981. The World Health Assembly Resolution in 1991 [1] to “eliminate leprosy as a public health problem” by the year 2000 galvanised extraordinary international support resulting in the fall in the point prevalence of patients registered for treatment of leprosy by over 90% to less than 1 in 10,000 at the global level. The effort was led by the World Health Organization (WHO) and supported by national governments and their health service staff, the Nippon Foundation, Novartis, the International Federation of Anti-Leprosy Organizations (ILEP), local non-governmental organizations (NGOs), and by people affected by leprosy. Since 2000, the focus has moved from prevalence of leprosy to incidence as measured by reported new case detection to sustain the achievements and to reduce the burden of disease, particularly on reduction and prevention of disability associated with leprosy and rehabilitation of those facing the long-term consequences of the disease [2].

Predicting neuropathy and reactions in leprosy at diagnosis and before incident events-results from the INFIR cohort study

Background Leprosy is a disease of skin and peripheral nerves. The process of nerve injury occurs gradually through the course of the disease as well as acutely in association with reactions. The INFIR (ILEP Nerve Function Impairment and Reactions) Cohort was established to identify clinically relevant neurological and immunological predictors for nerve injury and reactions. Methodology/Principal Findings The study, in two centres in India, recruited 188 new, previously untreated patients with multi-bacillary leprosy who had no recent nerve damage. These patients underwent a series of novel blood tests and nerve function testing including motor and sensory nerve conduction, warm and cold detection thresholds, vibrometry, dynamometry, monofilament sensory testing and voluntary muscle testing at diagnosis and at monthly follow up for the first year and every second month for the second year. During the 2 year follow up a total of 74 incident events were detected. Sub-clinical changes to nerve function at diagnosis and during follow-up predicted these new nerve events. Serological assays at baseline and immediately before an event were not predictive; however, change in TNF alpha before an event was a statistically significant predictor of that event. Conclusions/Significance These findings increase our understanding of the processes of nerve damage in leprosy showing that nerve function impairment is more widespread than previously appreciated. Any nerve involvement, including sub-clinical changes, is predictive of further nerve function impairment. These new factors could be used to identify patients at high risk of developing impairment and disability.

Comparing the Clinical and Histological Diagnosis of Leprosy and Leprosy Reactions in the INFIR Cohort of Indian Patients with Multibacillary Leprosy

Background The ILEP Nerve Function Impairment in Reaction (INFIR) is a cohort study designed to identify predictors of reactions and nerve function impairment in leprosy. The aim was to study correlations between clinical and histological diagnosis of reactions. Methodology/Principal Findings Three hundred and three newly diagnosed patients with World Health Organization multibacillary (MB) leprosy from two centres in India were enrolled in the study. Skin biopsies taken at enrolment were assessed using a standardised proforma to collect data on the histological diagnosis of leprosy, leprosy reactions and the certainty level of the diagnosis. The pathologist diagnosed definite or probable Type 1 Reactions (T1R) in 113 of 265 biopsies from patients at risk of developing reactions whereas clinicians diagnosed skin only reactions in 39 patients and 19 with skin and nerve involvement. Patients with Borderline Tuberculoid (BT) leprosy had a clinical diagnosis rate of reactions of 43% and a histological diagnosis rate of 61%; for patients with Borderline Lepromatous (BL) leprosy the clinical and histological diagnosis rates were 53.7% and 46.2% respectively. The sensitivity and specificity of clinical diagnosis for T1R was 53.1% and 61.9% for BT patients and 61.1% and 71.0% for BL patients. Erythema Nodosum Leprosum (ENL) was diagnosed clinically in two patients but histologically in 13 patients. The Ridley-Jopling classification of patients (n = 303) was 42.8% BT, 27.4% BL, 9.4% Lepromatous Leprosy (LL), 13.0% Indeterminate and 7.4% with non-specific inflammation. This data shows that MB classification is very heterogeneous and encompasses patients with no detectable bacteria and high immunological activity through to patients with high bacterial loads. Conclusions/Significance Leprosy reactions may be under-diagnosed by clinicians and increasing biopsy rates would help in the diagnosis of reactions. Future studies should look at sub-clinical T1R and ENL and whether they have impact on clinical outcomes.