Deciphering the Role of Post-Kala-Azar Dermal Leishmaniasis Patients in the Transmission of Leishmania Donovani: Implications for the Kala-Azar Elimination Program

Background: In the Indian subcontinent, visceral leishmaniasis (VL) incidence is on track to reach elimination goals by 2020 in nearly all endemic districts.  Although not included in official targets, previous data suggest post-kala-azar dermal leishmaniasis (PKDL) patients can act as an infection reservoir. Methods: We conducted xenodiagnosis of 47 PKDL and 15 kala-azar patients using laboratory-reared Phlebotomus argentipes.  In direct xenodiagnosis, flies were given access to the the patient's skin to feed for 15 minutes.  For indirect xenodiagnosis, flies were fed through a membrane on the patient's blood.  Five days later, blood-fed flies were dissected and examined by microscopy and/or PCR. A 3-mm skin snip biopsy (PKDL) or venous blood (kala-azar) was processed by quantitative PCR. Findings: Twenty-seven PKDL patients (57.4%) had positive results by direct and/or indirect xenodiagnosis.  Direct was significantly more sensitive than indirect xenodiagnosis (55.3% vs 6.4%, p 1 log10 unit higher than those with negative results (2.88 vs 1.66, p<0.0001).  In a multivariable model, parasite load, nodular lesions and positive skin microscopy were significantly associated with positive xenodiagnosis.  Blood parasite load was the strongest predictor for kala-azar.  Compared to kala-azar, nodular PKDL was more likely and macular PKDL less likely to result in positive xenodiagnosis, but neither difference reached statistical significance. Interpretation: Both nodular and macular PKDL can be infectious to sand flies. Active PKDL case detection and prompt treatment should be instituted and maintained as an integral part of VL control and elimination programs. Funding: This work was supported by the World Health Organization Special Programme for Research and Training in Tropical Diseases, Switzerland; Spanish Foundation for lnternational Cooperation, Health and Social Affairs; and icddr,b core donors. The funding sources had no role in the study design, collection, analysis and interpretation of the data, preparation of the manuscript, or the decision to submit for publication. Conflict of Interest: Dr. Bern reports personal fees from DNDi, outside the submitted work. All other authors: No reported conflicts of interest. Ethical Approval Statement: The protocol was approved by the Ethical Review Committee of ICDDR,B (#PR-14010). All patients provided written informed consent.