Post-exposure prophylaxis with single-dose rifampicin: from evidence to WHO guidelines
Some years ago, five health professionals working as professors in undergraduate courses and graduate programs at three Brazilian universities (University of Sao Paulo, State University of Mato Grosso and Federal University of Mato Grosso) joined efforts for the health needs of people with leprosy in Brazil.
This impact story for World Evidence-based Healthcare Day reports on a research project on post-exposure prophylaxis with single-dose rifampicin that resulted in the publication of a systematic review titled ‘Rifampicin chemoprophylaxis to prevent leprosy: a systematic review of quantitative and qualitative evidence’, which contributed to the 2018 World Health Organization guidelines for the diagnosis, treatment and prevention of leprosy.
Leprosy is a neglected tropical disease present in more than 120 countries, with a greater burden in India and Brazil. Currently, there are over 200,000 cases registered worldwide. It is a public health problem that can cause physical deformities and mental health problems, associated mainly with chronicity and stigma. Individuals in contact with patients with leprosy have an increased risk of disease exposure, which reinforces the need for chemoprophylactic measures, such as the use of rifampicin.
In 2014, the team’s proposal for a systematic review on single-dose rifampicin (SDR) as a post-exposure prophylaxis (PEP) strategy for leprosy contacts received financial support from the Brazilian Ministry of Health. The project was a response to a public call for a study on the evidence of the effects of immuno- and chemoprophylaxis of contacts of leprosy patients. At that time there was intense discussion about the need for new interventions and technologies to reduce the transmission of mycobacterium leprae and, consequently, reduce the burden of the disease worldwide. This sparked debates on the need for strategic partnerships between countries and international organisations to conduct operational research on the topic. The findings of a well-structured systematic review could guide institutions towards the adoption of more effective interventions.
At that time, the team understood the need to employ new evidence-based technologies to control the disease. The various studies published on the subject had not yet been brought together, synthesised or evaluated with the methodological rigor of a systematic review, which hindered clear and objective interpretation of the varying evidence. Moreover, the only published meta-analysis aggregated results were from heterogeneous protocols.
The team’s systematic review aimed to: (1) synthesise the best available evidence on the effectiveness of rifampicin chemoprophylaxis in preventing contacts (household, neighbourhood and community) of patients with leprosy from contracting the disease; and (2) synthesise the best available evidence on the experiences and acceptability of the preventive rifampicin therapy as reported by contacts and healthcare professionals who are in the practice of treating leprosy.
The review, published in 2017, reported a 56.5% reduction in the incidence of leprosy for contacts with the use of rifampicin in the first two years after contact with the disease. The combination of rifampicin and the Bacillus Calmette-Guérin (BCG) vaccine showed a protective effect of 80% against the disease. The review also indicated that chemoprophylaxis was a socially acceptable strategy as contacts and health professionals had a positive experience with the intervention.
The evidence from the systematic review, contributed to the WHO Global Leprosy guidelines of 2018. SDR combined with the BCG vaccine as a PEP is the strategy recommended by the World Health Organization (WHO) since 2018.
The recommendation was reinforced in a recent WHO publication (p.427): ‘The too slow decrease in the number of new cases in all countries will require interventions such as post-exposure prophylaxis (PEP) with single-dose rifampicin (SDR), as recommended in the WHO guidelines for the diagnosis, treatment and prevention of leprosy, in addition to strengthen case detection and effective contact tracing. The draft Global Leprosy Strategy for the period 2021–2030 is in line with “Ending the neglect to attain the Sustainable Development Goals – a road map for neglected tropical diseases 2021–2030”.’
Following the systematic review another research project, ‘Acceptability of chemoprophylaxis in an endemic area for leprosy: the PEP-Hans Brazil Project’ was conducted by two co-authors of the review to add to the qualitative findings of the systematic review, and to delve deeper into other questions about the managers' perspective on the applicability of using SDR in health services. The research project aimed to analyse the acceptability of chemoprophylaxis using SDR for contacts, index leprosy cases, and assess related factors that can influence adherence.
The two co-authors observed the acceptability of the intervention by health professionals, managers, contacts of leprosy cases and the community as something new for a leprosy program, and observed that it had the potential to reduce the risk of illness. A negative aspect observed was the lack of knowledge and confidence in the intervention by some health professionals. These findings were consistent with the systematic review.
This set of review and operational research studies provided the team with promising results and the expectation of implementation in healthcare services in Brazil. The team continues to study the effectiveness of SDR-PEP, seeking to understand immunological changes over time and age groups.
‘We believe that the synthesis of evidence using JBI’s systematic reviews of effectiveness methodology, and the acceptability of SDR-PEP enhanced scientific debate in the area and provided the team with support to argue for effective policies to reduce the burden of the disease in Brazil’, says Dr Silvana Ferreira. ‘We observed that the evidence produced through the systematic review strengthened our knowledge and facilitated the implementation of an innovative intervention with the potential to contribute to the reduction of leprosy cases.’
Dr Ferreira adds, ‘It is necessary to continually evaluate the new evidence that comes from studies under development, in addition to international efforts to adopt more effective measures to reduce the burden of the disease worldwide’.
The systematic review and research project were part of a body of work undertaken by the team, which also included work on the Leprosy Post Exposure Prophylaxis Programme and with the Global Partnership for Zero Leprosy.
Further Resources
Ferreira S, Yonekura T, Ignotti E, Oliviera L, Takahashi J, Soares C. Rifampicin chemoprophylaxis to prevent leprosy: a systematic review of quantitative and qualitative evidence. JBI Evid Synth. 2017;15(10):2555-84.
WHO. 2018 World Health Organization Guidelines for the diagnosis, treatment and prevention of leprosy. WHO; 2018.
Leprosy Post Exposure Prophylaxis Programme (InfoLep).
Global Partnership for Zero Leprosy
Authors
Ferreira, Silvana Margarida Benevides1,2; Ignotti, Eliane3,4; Soares, Cassia Baldini2,5; Sato, Camila Massae1; Cortela, Denise da Costa6
1. Graduate Program, Federal University of Mato Grosso, School of Nursing, Brazil
2. Brazilian Centre for Evidence-Based Healthcare: A JBI Centre of Excellence
3. Graduate Program in Environmental Sciences, State University of Mato Grosso, Brazil
4. Graduate Program in Health Sciences, Federal University of Mato Grosso, Brazil
5. Department of Collective Health Nursing, School of Nursing, University of São Paulo, Brazil
6. School of Medicine, State University of Mato Grosso, Brazil
References
World Health Organization Weekly Epidemiological Record (WER)
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