Leprosy Mailing List – July 27, 2023
Ref.: (LML) Reinfection as a major source of transmission
From: Joel Almeida, Mumbai, India
Dear Pieter and colleagues,
For several years now colleagues in endemic countries have been confronted with the accelerating accumulation of previously treated yet highly bacillated HD (leprosy) patients.
A recent article in IJDVL by Indian and Brazilian colleagues urges sufficient anti-microbial protection for HD (leprosy) patients with high bacillary loads. This is likely to benefit the patients as well as the population.
The information below seems to support those views. Once the facts are more clearly discerned, then it becomes difficult to deny sufficient anti-microbial protection to the highly bacillated polar LL (lepromatous) patients who otherwise are forced to suffer the depredations of the bacilli while serving unwillingly as major sources of transmission.
Best,
Joel Almeida
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The trend of HD over time
The Figure. Newly detected MB (multibacillary) HD cases in India over time, based on official reports. The evidence does not clearly demonstrate any steep decline.
Undetected MB cases seldom self-heal without sequelae. Therefore changes in case-finding frequency or intensity affect the cumulative detection rate of new PB cases more than of new MB cases. Therefore the annual new case detection rate (ANCDR) of MB cases is a more useful proxy indicator of transmission than the total ANCDR of all HD cases, albeit with some time lag.
Large endemic countries such as India, Brazil and Indonesia are yet to show any steep decline in HD incidence rate, even in zones such as Tocantins (Brazil) or Sampang, Bima and Sumenep (Indonesia) where single dose rifampicin was diligently given to household contacts of newly diagnosed HD patients.
Fact-based epidemiology, assembling clues and choosing persuasive hypotheses from the mass of evidence, is likely to break the demonstrable epidemiological stagnation by encouraging the kinds of interventions that achieved rapid decline of MB HD in even low income endemic areas. There is no substitute for learning from field projects with powerful epidemiological impact, and questioning interventions that have little or no epidemiological impact.
Recurrence rate among highly bacillated patients when MDT is prolonged
Among patients in India with a pre-treatment BI of 4+ or more, the recurrence rate of HD differed according to whether MDT was prolonged till smear negativity or withdrawn after only 24 months, A recurrence rate of only 1.27/100 patient-years of follow-up was found in the prolonged MDT group compared to 4.29/100 patient-years in the fixed 24 months MDT group (p<0.01).[1] Further, in an area of Brazil, the risk of recurrence was shown to be associated with the local endemicity of HD. For every new case reported among children aged 15 years or less, 2.41 cases of HD recurrence were reported among adults.[2]
Reinfection as an important cause of recurrence
The demonstrable association noted above between risk of recurrence and endemicity in a non-isolated, non-endogamous population is epidemiologically more consistent with exogenous reinfection than with endogenous relapse. The risk of reinfection is not expected to vary much according to various short durations of treatment (6 months or 7 months or 12 or even 24 months). But when highly bacillated patients in endemic areas are allowed to have anti-microbial protection for several years instead of only 24 months, then a large reduction is demonstrable in the risk of recurrent HD [1].
The occurrence of reinfection in HD has also been directly demonstrated using whole genome sequencing of bacilli.[3] In addition, genotyping of 19 human genetic markers in recurrent and non-recurrent HD cases suggested human genomic susceptibility to recurrence of HD.[4] LL patients with recurrence, if denied anti-microbial protection against reinfection, are capable of shedding as many as ten million viable bacilli per day or even per nose blow.[5] This astronomical number of bacilli shed by LL patients, with recurrent HD, is capable of driving transmission despite all other efforts. Moreover, expert clinicians have been reported to detect signs of recurrence five times more frequently than well trained but non-expert health workers.[6] Given the unavailability of expert clinicians in many places, it seems doubly advisable for highly bacillated patients to receive anti-microbial protection beyond 12 months. This is expected to reduce reinfection and limit the infectious pool, as evidenced by the rapid decline in the incidence rate of MB HD, LL (lepromatous) HD and all HD documented in Karigiri (Tamil Nadu, India) [7] Uele (DR Congo) [8] and Weifang/Shandong (China) [9] even at a time when those areas had conspicuously low incomes. All those projects provided prolonged anti-microbial protection for LL patients, which acts to reduce reinfection of LL patients and subsequent transmission.
Ping pong reinfection in endemic areas
By contrast to the successes noted above, when there are multiple persons with genomic susceptibility to LL HD in a single household or a single neighbourhood, then withdrawal of MDT after only 12 months or 24 months allows reinfection of previously treated anergic patients. Such "ping pong" reinfection between new "de novo" LL patients and previously treated polar LL patients, especially within households, can maintain transmission indefinitely. Such multiple LL case households and highly bacillated patients requiring retreatment have been reported from places such as Salaunikhurd village in Chhattisgarh, India, where the incidence rate of new cases climbed to as high as 10,000/million/year (1000/100,000 persons/yr).[10]
All this evidence supports the case for prolonged anti-microbial protection of highly bacillated patients in order to prevent reinfection and subsequent transmission. Prolonged anti-microbial protection also benefits the individual highly bacillated "slow responder" LL patient, as described in the article,
References
1. Girdhar BK, Girdhar A, Kumar A. Relapses in multibacillary leprosy: effect of length of therapy. Lepr Rev. 2000 Jun;71(2):144-53
2. Gonçalves FG, Belone AFF, Rosa PS, Laporta GZ.Underlying mechanisms of leprosy recurrence in the Western Amazon . BMC Infectious Diseases (2019) 19:460
3. Stefani MMA, Avanzi C, Buhrer-Sekula S, Benjak A, Loiseau C, Singh P Whole genome sequencing distinguishes between relapse and reinfection in recurrent HD cases. PLoS Negl Trop Dis 2017; 11: e0005598
4. Sartori PVU, Penna GO, Bührer-Sékula S et al. Human Genetic Susceptibility of Leprosy Recurrence. Scientific Reports 2020 volume 10, Article number: 1284
5. Davey TF, Rees RJ. The nasal dicharge in leprosy: clinical and bacteriological aspects. Lepr Rev. 1974 Jun;45(2):121-34
6. Balagon MF, Cellona RV, Cruz E, Burgos JA, Abalos RM, Walsh GP, et al. 2009. Long-term relapse risk in multibacillary leprosy after completion of 2 years of multiple drug therapy (WHO-MDT) in Cebu, Philipplines. Am. J Trop. Med. Hyg. 81(5), 895-899.
7. Norman G, Bhushanam JDRS, Samuel P. Trends in leprosy over 50 years in Gudiyatham Taluk, Vellore, Tamil Nadu. Ind J Lepr 2006. 78(2): 167-185. reviewed and analysed further in: 3a. Almeida J. Karigiri, India: How transmission rapidly was reduced in a low-income population. LML 29 Oct 2020
8. Tonglet R, Pattyn SR, Nsansi BN et al. The reduction of the leprosy endemicity in northeastern Zaire 1975/1989 J.Eur J Epidemiol. 1990 Dec;6(4):404-6 reviewed in: 4a. Almeida J. Reducing transmission in poor hyperendemic areas - evidence from Uele (DRC). LML 29 Nov 2019
9. Li HY, Weng XM, Li T et al. Long-Term Effect of Leprosy Control in Two Prefectures of China, 1955-1993. Int J Lepr Other Mycobact Dis. 1995 Jun;63(2):213-221. reviewed & analysed further in: 5a. Almeida J. What really happened in Shandong? LML 16 Nov 2019
10. Gitte S, Rewaria L, Santaram V, Jamil S. Descriptive Study of High Leprosy Endemic Pockets and Exploring Occurrence Factors of Multicase Families in the Village of Salaunikhurd of Chhattisgarh State. Int J Med. Public Health. 2021; 11(2):113-117
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << editorlml@gmail.com
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