Leprosy post-exposure prophylaxis in the Indian health system: A cost-effectiveness analysis.

India has the highest burden of leprosy in the world. Following a recent WHO guideline, the Indian National Leprosy Programme is introducing post-exposure prophylaxis with single-dose rifampicin (SDR-PEP) in all high-endemic districts of the country. The aim of this study is to estimate the long-term cost-effectiveness of SDR-PEP in different leprosy disability burden situations. We used a stochastic individual-based model (SIMCOLEP) to simulate the leprosy new case detection rate trend and the impact of implementing contact screening and SDR-PEP from 2016 to 2040 (25 years) in the Union Territory of Dadra Nagar Haveli (DNH) in India. Effects of the intervention were expressed as disability adjusted life years (DALY) averted under three assumption of disability prevention: 1) all grade 1 disability (G1D) cases prevented; 2) G1D cases prevented in PB cases only; 3) no disability prevented. Costs were US$ 2.9 per contact. Costs and effects were discounted at 3%. The incremental cost per DALY averted by SDR-PEP was US$ 210, US$ 447, and US$ 5,673 in the 25th year under assumption 1, 2, and 3, respectively. If prevention of G1D was assumed, the probability of cost-effectiveness was 1.0 at the threshold of US$ 2,000, which is equivalent to the GDP per capita of India. The probability of cost-effectiveness was 0.6, if no disability prevention was assumed. The cost per new leprosy case averted was US$ 2,873. Contact listing, screening and the provision of SDR-PEP is a cost-effective strategy in leprosy control in both the short (5 years) and long term (25 years). The cost-effectiveness depends on the extent to which disability can be prevented. As the intervention becomes increasingly cost-effective in the long term, we recommend a long-term commitment for its implementation.

Effect of a conditional cash transfer programme on leprosy treatment adherence and cure in patients from the nationwide 100 Million Brazilian Cohort: a quasi-experimental study.

BACKGROUND: Indirect financial costs and barriers to health-care access might contribute to leprosy treatment non-adherence. We estimated the association of the Brazilian conditional cash transfer programme, the Programa Bolsa Família (PBF), on leprosy treatment adherence and cure in patients in Brazil. METHODS: In this quasi-experimental study, we linked baseline demographic and socioeconomic information for individuals who entered the 100 Million Brazilian Cohort between Jan 1, 2007, and Dec 31, 2014, with the PBF payroll database and the Information System for Notifiable Diseases, which includes nationwide leprosy registries. Individuals were eligible for inclusion if they had a household member older than 15 years and had not received PBF aid or been diagnosed with leprosy before entering the 100 Million Brazilian Cohort; they were excluded if they were partial receivers of PBF benefits, had missing data, or had a monthly per-capita income greater than BRL200 (US$50). Individuals who were PBF beneficiaries before leprosy diagnosis were matched to those who were not beneficiaries through propensity-score matching (1:1) with replacement on the basis of baseline covariates, including sex, age, race or ethnicity, education, work, income, place of residence, and household characteristics. We used logistic regression to assess the average treatment effect on the treated of receipt of PBF benefits on leprosy treatment adherence (six or more multidrug therapy doses for paucibacillary cases or 12 or more doses for multibacillary cases) and cure in individuals of all ages. We stratified our analysis according to operational disease classification (paucibacillary or multibacillary). We also did a subgroup analysis of paediatric leprosy restricted to children aged up to 15 years. FINDINGS: We included 11 456 new leprosy cases, of whom 8750 (76·3%) had received PBF before diagnosis and 2706 (23·6%) had not. Overall, 9508 (83·0%) patients adhered to treatment and 10 077 (88·0%) were cured. After propensity score matching, receiving PBF before diagnosis was associated with adherence to treatment (OR 1·22, 95% CI 1·01-1·48) and cure (1·26, 1·01-1·58). PBF receipt did not significantly improve treatment adherence (1·37, 0·98-1·91) or cure (1·12, 0·75-1·67) in patients with paucibacillary leprosy. For patients with multibacillary disease, PBF beneficiaries had better treatment adherence (1·37, 1·08-1·74) and cure (1·43, 1·09-1·90) than non-beneficiaries. In the propensity score-matched analysis in 2654 children younger than 15 years with leprosy, PBF exposure was not associated with leprosy treatment adherence (1·55, 0·89-2·68) or cure (1·57, 0·83-2·97). INTERPRETATION: Our results suggest that being a beneficiary of the PBF, which facilitates cash transfers and improved access to health care, is associated with greater leprosy multidrug therapy adherence and cure in multibacillary cases. These results are especially relevant for patients with multibacillary disease, who are treated for a longer period and have lower cure rates than those with paucibacillary disease. FUNDING: CONFAP/ESRC/MRC/BBSRC/CNPq/FAPDF-Doenças Negligenciadas, the UK Medical Research Council, the Wellcome Trust, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES).

Household costs of leprosy reactions (ENL) in rural India.

BACKGROUND: Erythema nodosum leprosum (ENL) is a common immune-mediated complication of lepromatous (LL) and borderline lepromatous (BL) leprosy. Most patients experience chronic or multiple acute ENL over many years during an economically active period of their lives. Understanding the economic burden of ENL is essential to provide effective patient support, yet this area has not been investigated. METHODS: Ninety-one patients with LL or BL leprosy attending a leprosy hospital in Purulia district of West Bengal, India, were interviewed using a structured questionnaire. Cases (n = 53) were identified as those who had one or more episodes of ENL within the last 3 years. Controls (n = 38) had LL or BL leprosy but no history of ENL. Data were collected on household income, direct and indirect costs, and coping strategies. FINDINGS: The total household cost was Rs 1543 per month or 27.9% (IQR 13.2-52.6) of monthly household income for cases, and Rs 237 per month or 4.9% (IQR 1.7-13.4) of monthly household income for controls. Indirect costs accounted for 65% of total household costs for cases. Direct costs accounted for the remaining 35% of household costs, and resulted almost entirely from treatment-seeking in the private sector. Total household costs exceeded 40% of household income for 37.7% of cases (n = 20) and 2.6% of controls (n = 1) [1 USD = 59 INR]. INTERPRETATION: Households affected by ENL face significant economic burden and are at risk of being pushed further into poverty. Health policy should acknowledge the importance of private sector provision and the significant contribution to total household costs of lost productivity (indirect cost). Further work is needed to explore this area and identify solutions.

[Estimation of the execution of the national strategy of leprosy elimination in the "Hauts Bassins" region in Burkina Faso]. / Evaluation De La Mise En Oeuvre De La Strategie Nationale D'Elimination De La Lepre Dans La Region Des Hauts Bassins, Burkina Faso.

BACKGROUND: Burkina Faso achieved the leprosy elimination as a public health problem but this benefit was being lost. So, the National Program for Fighting against Leprosy has defined a strategy to reverse this situation. The aim of this survey was to evaluate the performance of the national program in the execution of this strategy in the region of "Hauts Bassins" (Burkina Faso) from 2005 to 2009. METHOD: The survey was led through the five sanitary districts of the region. It consisted in interview with the mean actors of leprosy control program and the analysis of the data notified on the leprosy cases, in order to estimate the progression of the key indicators of detection and follow-up care for patients having leprosy. RESULTS: During the survey period, 248 cases of leprosy were recorded including 236 new cases and 12 relapses. The prevalence of leprosy was 0.28 per 100 000 inhabitants in 2009. The detection rate decreased from 3.77 per 100 000 in 2005 to 2.75 per 100 000 in 2009. Among the 236 new cases of leprosy, 194 (82.2 %) were multibacillary form (MB). MB patients proportion increased from 69,3 % in 2005 to 91.1 % in 2009. The proportion of children was on average 3.8 %, the one of female cases 38.9 %. Newly diagnosed cases with grade 2 disabilities moved up from 21.4 % in 2005 to 42.2 % in 2009. The completion of cure rate was globally 88.26 %. The losts from follow-up among the patients who started multi-drug therapy were 7.14 %. CONCLUSION: The aim of the leprosy elimination as a public health problem is achieved but some challenges may be taken up, particularly in the organization of leprosy detection by the heath structures.

Cost-effectiveness of a chemoprophylactic intervention with single dose rifampicin in contacts of new leprosy patients.

BACKGROUND: With 249,007 new leprosy patients detected globally in 2008, it remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR) for contacts as chemoprophylactic intervention in the control of leprosy. METHODS: We conducted a single centre, double blind, cluster randomised, placebo controlled trial in northwest Bangladesh between 2002 and 2007, including 21,711 close contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to close contacts, with follow-up for four years. The main outcome measure was the development of clinical leprosy. We assessed the cost effectiveness by calculating the incremental cost effectiveness ratio (ICER) between the standard multidrug therapy (MDT) program with the additional chemoprophylaxis intervention versus the standard MDT program only. The ICER was expressed in US dollars per prevented leprosy case. FINDINGS: Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total, $6,009 incremental cost was invested and 38 incremental leprosy cases were prevented, resulting in an ICER of $158 per one additional prevented leprosy case. It was the most cost-effective in neighbours of neighbours and social contacts (ICER $214), slightly less cost-effective in next door neighbours (ICER $497) and least cost-effective among household contacts (ICER $856). CONCLUSION: Chemoprophylaxis with single dose rifampicin given to contacts of newly diagnosed leprosy patients is a cost-effective intervention strategy. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world.

Treating leprosy: an Erb-al remedy?

The leprosy pathogen Mycobacterium leprae attacks Schwann cells in the peripheral nervous system, causing them to demyelinate. Recent work by Tapinos et al. shows that a direct mechanism of demyelination induced by M. leprae depends on the binding of the bacterium to the receptor tyrosine kinase ErbB2 on Schwann cells and the resulting activation of the Ras-Raf-MEK-ERK pathway. These findings have relevance for the potential treatment of leprosy and they highlight parallels between the dedifferentiation signal in leprosy and that in nerve injury and cancer.

Chemoprophylaxis is effective in the prevention of leprosy in endemic countries: a systematic review and meta-analysis. MILEP2 Study Group. Mucosal Immunology of Leprosy.

OBJECTIVE: To quantify the efficacy of chemoprophylaxis against leprosy. METHOD: Literature searching of Medline and Embase databases, hand-searching of references and correspondence with investigators. STUDY SELECTION: published papers relating to the prevention of leprosy and the use of chemotherapy in leprosy were identified for critical appraisal. Trials were selected and grouped into three categories according to study design and control groups. DATA ANALYSIS: the relative risks (RR) with 95% confidence intervals were calculated from the original data using a random effects model. To assess the cost-effectiveness of chemoprophylaxis, a further analysis of the rates of disease in the trial and control groups was done based on the numbers needed to be treated (NNT) to prevent one new case of leprosy. RESULTS: A total of 14 trials were identified from 127 published papers on chemoprophylaxis of leprosy. The trials were categorized into randomized controlled trials, non-randomized controlled trials, and uncontrolled trials. The overall results of the meta-analysis shows that chemoprophylaxis gives around 60% protection against leprosy. The NNT are low in trials of household contacts. CONCLUSIONS: The evidence shows that chemoprophylaxis against leprosy is an effective way to reduce the incidence of leprosy, particularly in household contacts. The role of chemoprophylaxis needs to be re-examined using newer drugs given the continuing case detection rates globally.

Socioeconomics of a global leprosy eradication programme.

In the absence of evidence in the literature on cost factors in the management of leprosy, a reference is made to the sporadic attempts to study costs of case detection and treatment. Such studies indicate that in the currently declining phase of leprosy endemicity, employing a conventionally trained, salaried class of paramedical staff for field surveys is prohibitively expensive if cost per case detected is computed. Involving primary healthcare and community derived workers is cost effective. Likewise, short course chemotherapy with newer drugs under trial, administered under supervision by community volunteers, reduces the expenses considerably. Community-based disability services using inexpensive tools may cut costs by 90%. Operational research on cost effectiveness of rehabilitation comparing 'integrated' with 'vertical' approaches is, unfortunately, still in a primitive stage. It is urged that in view of the changing logistics, manpower costs and financial implications should be given serious consideration by health planners. Post-elimination problems such as: (i) unearthing hidden cases; (ii) community-based supervised treatment with highly promising newer drugs; (iii) identification of reactions and relapses; and (iv) field management of disabilities resulting from acute and silent neuritis etc could be solved in a much cheaper manner. Integration of leprosy into general healthcare services and community-based rehabilitation of leprosy patients along with those disabled by other diseases will be the major task in future as these procedures are expected to reduce management costs and eliminate stigma.

Elimination of leprosy as a public health problem: progress and prospects.

Leprosy is still an important problem in about 80 countries of Asia, Africa and Latin America, some 2.4 million persons being estimated to have the disease in 1994. The WHO-recommended standard multidrug therapy (MDT) was introduced in the 1980s and has been shown to be effective in combating the disease. Experiences based on many thousands of patients treated with MDT over the past decade indicate extremely low relapse rates (cumulative relapse rates around 1%). By the end of 1993, some 5.6 million patients had been cured, and the global cumulative MDT coverage of registered patients had reached 89%. The number of registered cases fell from 5.4 million in 1985 to 1.7 million in 1994. The significant progress made in leprosy control enabled the World Health Assembly in 1991 to set a goal for eliminating leprosy as a public health problem by the year 2000. One important epidemiological factor is that leprosy is very unevenly distributed: 80% of the problem is confined to only five countries and 92% to just 25 countries. The elimination strategy envisages identifying and treating with MDT a total of about 5 million cases from 1994 to the year 2000. The cost of dealing with these cases has been estimated at US$ 420 million, including US$ 150 million for the drugs.

PIP: The World Health Organization-recommended standard multidrug therapy (MDT) against leprosy was introduced in the 1980s and has since been extremely effective against the disease. The number of registered cases worldwide fell from 5.4 million in 1985 to 1.7 million in 1994, the global cumulative MDT coverage of registered patients was at 89%, and the cumulative relapse rates have been low at around 1%. Leprosy, however, remains an important problem in about 80 countries in Asia, Africa, and Latin America, with 2.4 million people estimated to be with the disease in 1994. 80% of the problem is confined to five countries and 92% to just 25 countries. The prevalence of leprosy is therefore far from evenly distributed. The largest numbers of registered cases are in India, Brazil, Indonesia, and Myanmar at 995,285, 223,539, 70,961, and 56,410, respectively. The highest prevalences per 10,000 population are in Brazil, Myanmar, Chad, and India at 14.30, 12.98, 12.43, and 11.34, respectively. Progress against leprosy prompted the World Health Assembly in 1991 to establish the goal of eliminating leprosy as a public health problem by the year 2000. Eliminated is defined as less than one case per 10,000 population. The strategy to that end envisages identifying and treating with MDT about five million cases of leprosy from 1994 to the year 2000 at an estimated cost of $420 million, including $150 million for the drugs.