A Review of the Efficacy, Safety, and Feasibility of Rifamycin-Based Post-Exposure Chemoprophylaxis for Leprosy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Literature Search
2.2. Data Presentation
3. Results
3.1. Literature Review
3.2. Post-Exposure Chemoprophylaxis
3.2.1. Evidence for Efficacy of Single Agent Rifamycin-Based Chemoprophylaxis Regimens
First Author | Year Published | Location | Study Design | Study Population | Chemoprophylaxis Regimen | No. of Contacts Included | Duration of Follow-Up | Estimated Efficacy | Comments |
---|---|---|---|---|---|---|---|---|---|
Completed rifamycin monotherapy studies | |||||||||
Cartel [21] | 1992 | Marquesas Islands | Uncontrolled trial | Endemic population | SDR
| 5895 | 4 years | 40–50% | Small case numbers Susceptible to confounding |
Nguyen [22] | 2000 | 10 years | 35–40% | ||||||
Bakker [17] | 2005 | Indonesia | Controlled clinical trial | Endemic population (contact group, blanket group + control group) | Two doses of rifampicin 3.5 months apart
| 3965 | 33.5 months | HR 0.25 (95% CI 0.068–0.95) in blanket group compared to control group (p = 0.031) | No difference between contact and control groups (p = 0.93) |
Moet [7] | 2008 | India | Cluster randomised controlled trial | Household + neighbour contacts | SDR (weight-based)
| 28,092 | 4 years | 57% (95% CI 32.9%–71.9%) overall reduction in incidence at 2 years (p = 0.0002) | NNT = 265 (95% CI 176–537) Benefit less in HHC + contacts of MB cases |
Khoudri [24] | 2018 | Morocco | Retrospective time series analysis | Household contacts | SDR (age/weight-based dosing)
| 4019 screened 3704 received SDR | 12 years | 16% per year reduction in NCDR following SDR-PEP introduction (p = 0.05) | Multiple limitations Possible confounding |
Wang [25] | 2023 | China | Cluster randomised controlled trial | Household contacts | Single-dose rifapentine or rifampicin
| 2331 Rifapentine 2760 Rifampicin 2359 Control | 4 years | Cumulative incidence ratio 0.16 (95% CI 0.03–0.87) in rifapentine group compared to control group (p = 0.02) | No significant difference in cumulative incidence between rifampicin and control group (p = 0.23). No adverse events recorded |
Hasker [26] | 2024 | Madagascar and Comoros | Cluster randomised trial |
| Single double-dose rifampicin (20 mg/kg) | 110,666 | Madagascar: 2 years Comoros: 3 years | Arm 2 (IRR 0.95, 95% CI 0.4–2.23) Arm 3 (IRR 0.80, 95% CI 0.34–1.87) Arm 4 (IRR 0.58, 95% CI 0.22–1.56)
| IRR 0.35 (95% CI 0.15–0.82) in HHC on subgroup analysis NNT = 82 for HHC compared to 870 for study population as a whole |
Active rifamycin monotherapy studies | |||||||||
Schoenmakers [27] | Protocol published 2021 | Multiple countries | Cluster randomised trial | Endemic districts within countries
| Single-dose rifampicin (150–600 mg) | Calculated sample size:
| 2 years | - | |
Coleman [28] | Protocol published 2023 | Kiribati | Implementation study | Endemic population
| SDR (Age/weight-based dosing)
| 64,439 | 3 years | - | |
Completed studies of combination rifamycin-based regimens | |||||||||
Diletto [29] | 1999 | Federated States of Micronesia | Uncontrolled trial | Endemic population
| Rifampicin 600 mg, ofloxacin 400 mg + Minocycline 100 mg | 105,506 total
| 2 years | Impact of chemoprophylaxis on incidence not determined as part of this study | Reduction of cases between subsequent rounds but not possible to separate effects of case finding/treatment from screening/prophylaxis. Relative risk of clinical disease lower in chemoprophylaxis group |
Daulako [30] | 1999 | Kiribati | Implementation study | Endemic population
| Rifampicin 600 mg, ofloxacin 400 mg + minocycline 100 mg | 32,645 total for two islands
| 1 year | Impact of chemoprophylaxis on incidence not determined as part of this study. | Good safety profile of regimen with low rates of adverse events. |
Tin [31] | 1999 | Marshall Islands | Implementation study | Household contacts | Rifampicin 600 mg, ofloxacin 400 mg + Minocycline 100 mg | 2831
| - | Impact of chemoprophylaxis on incidence not determined as part of this study | Good safety profile of regimen with low rates of adverse events. |
Khaing [32] | 2009 | Myanmar | Randomised trial
| Household contacts
|
| 152 contacts
| 6 months | Efficacy of chemoprophylaxis not assessed as part of this study | Significant reduction in PGL-1 titres in adults but not in children. Non-significant reduction seen overall. |
Oo [33] | 2008 | Myanmar | Randomised controlled trial
| Household and neighbour contacts in endemic community |
| 829 extended contacts | 2 years | Efficacy of chemoprophylaxis not assessed as part of this study | Significant reduction in mean antibody titres in adults but not in children 2 years post chemoprophylaxis |
Astari [34] | 2021 | Indonesia | Cohort study | Elementary school children
|
| 2548 screened
| 5 years | No progression to leprosy at 5 years | Significant reduction in PGL-1 antibody titres over study period No comparator group |
Active studies of combination rifamycin-based regimen | |||||||||
Hinders [35] | Protocol published 2023 | Multiple countries | PEP ++ Cluster randomised controlled trial | Endemic populations
| Intervention arm:
| Calculated required sample size of 202,360 | 2 years | - | |
Younoussa [36] | Protocol published 2024 | Madagascar + Comoros | BE-PEOPLE cluster randomised controlled trial | Endemic population
| Intervention arm
Rifampicin 150–600 mg | Calculated required sample size of 124,000 | 3 years | - |
3.2.2. Combination/Enhanced Rifamycin-Based Chemoprophylaxis Regimens
3.2.3. Safety
3.2.4. Promotion of Antimicrobial Resistance
3.2.5. Feasibility and Acceptability of Rifamycin-Based Chemoprophylaxis
3.2.6. Modelling
3.2.7. Implementation and Cost Effectiveness of Chemoprophylaxis Programmes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Campbell, P.O.; Douglas, N.M.; Chambers, S.T. A Review of the Efficacy, Safety, and Feasibility of Rifamycin-Based Post-Exposure Chemoprophylaxis for Leprosy. Trop. Med. Infect. Dis. 2025, 10, 84. https://doi.org/10.3390/tropicalmed10040084
Campbell PO, Douglas NM, Chambers ST. A Review of the Efficacy, Safety, and Feasibility of Rifamycin-Based Post-Exposure Chemoprophylaxis for Leprosy. Tropical Medicine and Infectious Disease. 2025; 10(4):84. https://doi.org/10.3390/tropicalmed10040084
Chicago/Turabian StyleCampbell, Patrick O., Nicholas M. Douglas, and Stephen T. Chambers. 2025. "A Review of the Efficacy, Safety, and Feasibility of Rifamycin-Based Post-Exposure Chemoprophylaxis for Leprosy" Tropical Medicine and Infectious Disease 10, no. 4: 84. https://doi.org/10.3390/tropicalmed10040084
APA StyleCampbell, P. O., Douglas, N. M., & Chambers, S. T. (2025). A Review of the Efficacy, Safety, and Feasibility of Rifamycin-Based Post-Exposure Chemoprophylaxis for Leprosy. Tropical Medicine and Infectious Disease, 10(4), 84. https://doi.org/10.3390/tropicalmed10040084