• 1.

    WHO Fact Sheet, 2020. WHO Fact Sheet on Leishmaniasis. Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis. Accessed March 10, 2020.

    • Search Google Scholar
    • Export Citation
  • 2.

    Karunaweera ND, Ginige S, Senanayake S, Silva H, Manamperi N, Samaranayake N, Siriwardana Y, Gamage D, Senerath U, Zhou G, 2020. Spatial epidemiologic trends and hotspots of leishmaniasis, Sri Lanka, 2001–2018. Emerg Infect Dis 26: 110.

    • Search Google Scholar
    • Export Citation
  • 3.

    Karunaweera ND, Pratlong F, Siriwardane HVYD, Ihalamulla RL, Dedet JP, 2003. Sri Lankan cutaneous leishmaniasis is caused by Leishmania donovani zymodeme MON-37. Trans R Soc Trop Med Hyg 97: 380381.

    • Search Google Scholar
    • Export Citation
  • 4.

    Siriwardana H, Chandrawansa PH, Sirimanna G, Karunaweera ND, 2012. Leishmaniasis in Sri Lanka: a decade old story. Sri Lanka J Infect Dis 2: 212.

    • Search Google Scholar
    • Export Citation
  • 5.

    Ranasinghe S, Zhang WW, Wickremasinghe R, Abeygunasekera P, Chandrasekharan V, Athauda S, Medis S, Hulangamuwa S, Matlashewski G, Pratlong F, 2012. Leishmania donovani zymodeme MON-37 isolated from an autochthonous visceral leishmaniasis patient in Sri Lanka. Pathog Glob Health 106: 421424.

    • Search Google Scholar
    • Export Citation
  • 6.

    Siriwardana HVYD, Karunanayake P, Goonerathne L, Karunaweera ND, 2017. Emergence of visceral leishmaniasis in Sri Lanka: a newly established health threat. Pathog Glob Health 111: 317326.

    • Search Google Scholar
    • Export Citation
  • 7.

    Kariyawasam KKGDUL, Selvapandiyan A, Siriwardana HVYD, Dube A, Karunanayake P, Senanayake SASC, Dey R, Gannavaram S, Nakhasi HL, Karunaweera ND, 2018. Dermotropic Leishmania donovani in Sri Lanka: visceralizing potential in clinical and preclinical studies. Parasitology 145: 443452.

    • Search Google Scholar
    • Export Citation
  • 8.

    Sri Lanka College of Dermatologists, 2013. Guidelines on Management of Leishmaniasis. Colombo, Sri Lanka: Sri Lanka College of Dermatologists.

    • Search Google Scholar
    • Export Citation
  • 9.

    Refai WF, Madarasingha NP, Sumanasena B, Weerasingha S, De Silva A, Fernandopulle R, Satoskar AR, Karunaweera ND, 2017. Efficacy, safety and cost-effectiveness of thermotherapy in the treatment of Leishmania donovani-induced cutaneous leishmaniasis: a randomized controlled clinical trial. Am J Trop Med Hyg 97: 11201126.

    • Search Google Scholar
    • Export Citation
  • 10.

    Reithinger R, Mohsen M, Wahid M, Bismullah M, Quinnell RJ, Davies CR, Kolaczinski J, David JR, 2005. Efficacy of thermotherapy to treat cutaneous leishmaniasis caused by Leishmania tropica in Kabul, Afghanistan: a randomized, controlled trial. Clin Infect Dis 40: 11481155.

    • Search Google Scholar
    • Export Citation
  • 11.

    López L, Robayo M, Vargas M, Vélez ID, 2012. Thermotherapy. An alternative for the treatment of American cutaneous leishmaniasis. Trials 13: 58.

  • 12.

    Bumb RA, Prasad N, Khandelwal K, Aara N, Mehta RD, Ghiya BC, Salotra P, Wei L, Peters S, Satoskar A, 2013. Long-term efficacy of single-dose radiofrequency-induced heat therapy vs. intralesional antimonials for cutaneous leishmaniasis in India. Br J Dermatol 168: 11141119.

    • Search Google Scholar
    • Export Citation
  • 13.

    Valencia BM, Miller D, Witzig RS, Boggild AK, Llanos-Cuentas A, 2013. Novel low-cost thermotherapy for cutaneous leishmaniasis in Peru. PLoS Negl Trop Dis 7: 19.

    • Search Google Scholar
    • Export Citation
  • 14.

    Lobo IMF, Soares MBP, Correia TM, de Freitas LAR, Oliveira MI, Nakatani M, Netto E, Badaro R, David JR, 2006. Heat therapy for cutaneous leishmaniasis elicits a systemic cytokine response similar to that of antimonial (glucantime) therapy. Trans R Soc Trop Med Hyg 100: 642649.

    • Search Google Scholar
    • Export Citation
  • 15.

    Shah SA, Memon AA, Auwj-E-Shamim, Baqi S, Witzig R, 2014. Low-cost thermotherapy for cutaneous leishmaniasis in Sindh, Pakistan. J Pak Med Assoc 64: 13981404.

    • Search Google Scholar
    • Export Citation
  • 16.

    Aronson NE 2010. A randomized controlled trial of local heat therapy versus intravenous sodium stibogluconate for the treatment of cutaneous Leishmania major infection. PLoS Negl Trop Dis 4: e628.

    • Search Google Scholar
    • Export Citation
  • 17.

    Safi N, Davis G, Nadir M, Hamid H, Robert LCA, 2012. Evaluation of thermotherapy for the treatment of cutaneous Leishmaniasis in Kabul, Afghanistan: a randomized controlled trial. Int J Infect Dis 16: e174.

    • Search Google Scholar
    • Export Citation
  • 18.

    Kämink S, Abdi A, Kamau C, Ashraf S, Ansari MA, Qureshi NA, Schalling H, Grobusch MP, Fernhout J, Ritmeijer K, 2019. Failure of an innovative low-cost, noninvasive thermotherapy device for treating cutaneous leishmaniasis caused by Leishmania tropica in Pakistan. Am J Trop Med Hyg 101: 13731379.

    • Search Google Scholar
    • Export Citation
  • 19.

    Refai FW, Madarasingha NP, Fernandopulle R, Karunaweera N, 2016. Nonresponsiveness to standard treatment in cutaneous leishmaniasis: a case series from Sri Lanka. Trop Parasitol 6: 155158.

    • Search Google Scholar
    • Export Citation
  • 20.

    Ponte-Sucre A, Gamarro F, Dujardin JC, Barrett MP, López-Vélez R, García-Hernández R, Pountain AW, Mwenechanya R, Papadopoulou B, 2017. Drug resistance and treatment failure in leishmaniasis: a 21st century challenge. PLoS Negl Trop Dis 11: 124.

    • Search Google Scholar
    • Export Citation
  • 21.

    Siriwardana Y, Deepachandi B, Gunasekara C, Warnasooriya W, Karunaweera ND, 2019. Leishmania donovani induced cutaneous leishmaniasis: an insight into atypical clinical variants in Sri Lanka. J Trop Med 2019: 4538597.

    • Search Google Scholar
    • Export Citation
  • 22.

    Ranawaka RR, Weerakoon HS, de Silva SHP, 2015. Randomized, double-blind, controlled, comparative study on intralesional 10% and 15% hypertonic saline versus intralesional sodium stibogluconate in Leishmania donovani cutaneous leishmaniasis. Int J Dermatol 54: 555563.

    • Search Google Scholar
    • Export Citation
  • 23.

    Kariyawasam UL 2017. Genetic diversity of Leishmania donovani that causes cutaneous leishmaniasis in Sri Lanka: a cross sectional study with regional comparisons. BMC Infect Dis 17: 791.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

Therapeutic Response to Thermotherapy in Cutaneous Leishmaniasis Treatment Failures for Sodium Stibogluconate: A Randomized Controlled Proof of Principle Clinical Trial

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  • 1 Department of Parasitology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka;
  • 2 Base Hospital, Tangalle, Sri Lanka;
  • 3 District General Hospital Hambantota, Hambantota, Sri Lanka;
  • 4 Teaching Hospital Anuradhapura, Anuradhapura, Sri Lanka;
  • 5 General Sir John Kotelawala Defence University, Dehiwala-Mount Lavinia, Sri Lanka

ABSTRACT

Treatment failure to intralesional sodium stibogluconate (IL-SSG) is a health challenge for cutaneous leishmaniasis (CL) in Sri Lanka. A randomized controlled proof of principle clinical trial, with two arms (viz., radio frequency–induced heat therapy [RFHT] by a ThermoMed™ device (Model 1.8, Thermosurgery Technologies, Inc., Phoenix, AZ) and thermotherapy by a handheld exothermic crystallization thermotherapy for CL [HECT-CL] device) was conducted on 40 CL treatment failures to IL-SSG, from three hospitals in Tangalle, Hambantota, and Anuradhapura, from January 2017 to January 2018, followed up for 180 days post-thermotherapy with a final follow-up in February 2020. Intention-to-treat cure rates were calculated at day 90 (initial cure rate) and at day 180 (final cure rate) posttreatment. Radio frequency–induced heat therapy group: the initial cure rate was 100% (20/20) and the final cure rate was 95% (19/20), with one patient relapsing. The HECT-CL group: both the initial and final cure rates were 80% (16/20), with no relapses and one excluded from the trial. In February 2020 (1.6–3 years posttreatment), 27 traceable patients (RFHT = 16, HECT-CL = 11) remained healed. Second-degree burns were observed with RFHT in 65% (13/20), with HECT-CL in 15% (3/20), which completely resolved subsequently. The cure rates between the two treatment groups were comparable (P = 0.15). Radio frequency–induced heat therapy consumed less time and required only a single hospital visit. Handheld exothermic crystallization thermotherapy for CL is potentially usable at community settings with both being less costly than IL-SSG. This study is the first proof that thermotherapy is an efficacious and safe treatment for CL patients in Sri Lanka, complicated by treatment failure to IL-SSG.

Author Notes

Address correspondence to Nadira Karunaweera, Department of Parasitology, Faculty of Medicine, University of Colombo, 25, Kynsey Road, Colombo 8, Sri Lanka, 00800. E-mail: nadira@parasit.cmb.ac.lk

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID, NIH, or the University of Colombo.

Financial support: This study was supported by the University of Colombo research grant (AP/3/2/2016/SG/13) to Hermali Silva and the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH, USA, under award number R01AI099602 and U01AI136033 to Nadira Karunaweera.

Authors’ addresses: Hermali Silva, Sudath Weerasingha, and Nadira Karunaweera, Department of Parasitology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka, E-mails: hermali@parasit.cmb.ac.lk or hermalisilva@gmail.com, sudathws@yahoo.com, and nadira@parasit.cmb.ac. Achala Liyanage, Department of Community Medicine, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka, E-mail: achalaliyanage@yahoo.com. Theja Deerasinghe, District General Hospital Embilipitiya, Embilipitiya, Sri Lanka, E-mail: athdeerasinghe@yahoo.com. Buthsiri Sumanasena and Deepani Munidasa, Teaching Hospital Anuradhapura, Anuradhapura, Sri Lanka, E-mails: jam.buth@yahoo.com and deepanimunidasa@yahoo.com. Hiromel de Silva, District General Hospital Matara, Matara, Sri Lanka, E-mail: virajine@gmail.com. Rohini Fernandopulle, General Sir John Kotelawala Defence University, Rathmalana, Sri Lanka, E-mail: rohinifernandopulle@gmail.com.

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