The saga of the elimination of Hansen's Disease as a public health problem

por Claudio Guedes Salgado.

Federal University of ParáPresident of the Brazil Hansen's Disease Society (Sociedade Brasileira de Hansenologia)

When I was preparing to start writing this article, I received test results for a person affected by Hansen’s disease who was hospitalised. A 60-year-old patient, with ‘peripheral polyneuritis’ who was being treated for ischemic stroke, diagnosed with Lucio's phenomenon, after a colleague noticed a face with madarosis and infiltrated ears.

Hansen’s disease (HD) was officially declared "eliminated as a public health problem" by the World Health Organisation (WHO) in 2000 (1). In 1982, WHO recommended the introduction of multidrug therapy (MDT), a regimen used to date which comprises, for multibacillary (MB) HD, monthly rifampicin, daily dapsone and clofazimine for 24 months or until smears are negative or, for paucibacillary (PB) HD, monthly rifampicin and daily dapsone for 6 months (2). While the USA maintained their daily dose regimen of these drugs, the WHO indicated rifampicin in a single monthly dose, maintaining the other two drugs for daily use. There are reports in the literature that this would have been a decision based more on financial costs than on scientific results (3), and the report recommending MDT in 1982 itself refers to rifampicin as a high-cost drug (2).

In the early 1980s there were more than 5 million 'cumulative cases', i.e. people who had been registered and who had not been removed from the register. With the advent of MDT and a fixed minimum period of treatment, people affected by Hansen’s disease could be cured and released from treatment (RFT) after receiving MDT for a fixed period of time. Sufficient criteria for cure? No. Neither bacilloscopic, given that treatment completion is defined by the number (24) of doses, nor clinical, considering that patients with some degree of physical disability are discharged, together with those who experience the reactions which are only understood as a result of some imbalance in the immune system. In reality, persons affected by HD are discharged after a fixed 12-dose regimen, despite important differences in reactions compared to the 24-dose regimen (4). The result? Nobody knows how many people in the world are living with some physical disability caused by Hansen’s disease or how many patients experience a reaction after RFT, or ‘cure by discharge’.

In the early 1990s, with the apparent success of MDT, WHO set the year 2000 as the target for elimination and countries committed themselves to reaching less than 1 case per 10,000 population (5). With the systematic roll-out of training, the world went from almost 600,000 new cases per year in 1991 to more than 800,000 in 1998, the highest level ever attained. This was two years before the elimination target, defined by prevalence, a measure that had been in continuous decline since the early 1990s because of fixed-duration treatment, RFT (cured by discharge) even for patients with impairments or reactions, and ‘tidying up’ of Hansen’s disease registers (6).

In 2001, the only two major countries where Hansen’s disease had not been eliminated as a public health problem were India and Brazil. But these countries would be given a second chance, for the year 2005. India's numbers from 2001 onwards fall sharply, year on year. Since at least 1993, India maintained an annual detection rate of more than 400,000 new cases. In 2001 there were 473,658 new cases. In 2005, only 161,457. With prevalence declining in line with the detection of new cases, Hansen’s disease was eliminated in India. Brazil remained the only country in the world not to achieve ‘elimination’, even though incidence fell from 49,384 cases in 2004 to 38,410 in 2005 (7).

The target of less than 1 case per 10,000 population to eliminate Hansen’s disease as a public health problem is not a ‘magic number’. There is no clear definition of what constitutes a public health problem for all countries involved, and consequently no evidence to demonstrate that public health would no longer be impacted once this number was reached. WHO says that, from below 1 case per 10,000 inhabitants, the disease would tend to die out (8). Compounding this, in 1998 the WHO indicated a reduction of MDT from 24 to only 12 doses for MB patients, also with very little scientific data of good quality to support the change (9).

Therapeutic failure, bacterial persistence, drug resistance, relapse, the possibility of different strains circulating – important factors relevant to eliminating bacterial disease - were not considered in decisions taken for a chronic, long-term disease where actions in one decade confer serious problems in the following decades.

Throughout this period, significant advances have been achieved by science, particularly in serology and molecular biology, electromyoneurography, and ultrasonography. All these techniques can increase significantly the sensitivity of the only complementary examination available today, the skin slit smear. The widespread and consistent use of these techniques would test WHO's hypothesis of Hansen’s disease elimination, which has never really been tested (10).

These issues are about new cases and ignore the 2-3 million people living with physical disabilities caused by Hansen’s disease and the 4 million cases of Hansen’s disease predicted in 2015 to have accumulated by 2020 (11). Taken together, we are back to where we were in 1980, with well over 5 million people affected by Hansen’s disease.

Finally, if we add to the total all those who are RFT (cured by discharge) but with therapeutic insufficiency or therapeutic failure, whether due to persistence of the bacilli, drug resistance, or problems in drug metabolism, contributing silently to the maintenance of endemicity in the community, the numbers become even worse. It is time to look seriously at the problem, and to free the world from the stagnation that endemic Hansen’s disease has become.

References

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  2. Chemotherapy of leprosy for control programmes. World Heal Organ - Tech Rep Ser [Internet]. 1982 [cited 2020 Oct 5];675:1–33. Available from: https://pubmed.ncbi.nlm.nih.gov/6806990/

  3. Dacso MM, Jacobson RR, Scollard DM, Stryjewska BM, Prestigiacomo JF. Evaluation of multi-drug therapy for leprosy in the United States using daily rifampin. South Med J. 2011;104(10):689–94.

  4. Balagon MVF, Gelber RH, Abalos RM, Cellona R V. Reactions following completion of 1 and 2 year multidrug therapy (MDT). Am J Trop Med Hyg [Internet]. 2010 Sep [cited 2020 Oct 5];83(3):637–44. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929063/

  5. World Health Assembly 44. Forty-fourth World Health Assembly, Geneva, 6-16 May 1991: resolutions and decisions, annexes. 1991; Available from: https://apps.who.int/iris/handle/10665/173858

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  7. Global leprosy situation, 2006. Relev épidémiologique Hebd / Sect d’hygiène du Secrétariat la Société des Nations = Wkly Epidemiol Rec / Heal Sect Secr Leag Nations [Internet]. 2006 Aug 11 [cited 2020 Oct 5];81(32):309–16. Available from: https://pubmed.ncbi.nlm.nih.gov/16903018/

  8. WHO | Elimination of leprosy FAQ [Internet]. [cited 2020 Oct 5]. Available from: https://www.who.int/lep/strategy/faqs/en/

  9. World Health Organization (WHO). WHO Expert Committee on Leprosy (‎1997: Geneva, Switzerland)‎ & World Health Organization. WHO Expert Committee on Leprosy: seventh report [Internet]. WHO technical report series; 874. World Health Organization; 1998. Available from: https://apps.who.int/iris/handle/10665/42060

  10. Salgado CG, Barreto JG, Silva MB da, Goulart IMB, Barreto JA, Junior NF de M, et al. Are leprosy case numbers reliable? Lancet Infect Dis [Internet]. 2018 Feb 1 [cited 2018 Jan 26];18(2):135–7. Available from: http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30012-4/fulltext#.WmqVq2P8oBM.mendeley

  11. Smith WC, van Brakel W, Gillis T, Saunderson P, Richardus JH. The Missing Millions: A Threat to the Elimination of Leprosy. PLoS Negl Trop Dis. 2015;9(4).