Rhesus monkey model for Leishmania major transmitted by Phlebotomus papatasi sandfly bites

Leishmaniasis research needs a near-human model for investigations of natur al infection processes, immunological responses and evaluation of treatment s. Therefore, we developed a reproducible system using Leishmania major Yak imoff & Schokhor (Trypanosomatidae: Kinetoplastida), the cause of Old World zoonotic cutaneous leishmaniasis (ZCL), transmitted to rhesus monkeys Maca ca mulatta (Zimmerman) (Primates: Cercopithecidae) by sandfly bites of expe rimentally infected Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae). Eight monkeys of presumed Indian origin (Leishmania naive) were exposed to bites of female sandflies that had been infected with L. major by membrane- feeding on human blood seeded with amastigotes isolated from hamster footpa d lesions. Infection rates of membrane-fed sandflies averaged >85% seven da ys after the infective feed, with uniformly high numbers of promastigotes i n the stomodaeal valve region of the sandfly gut. Nodules and ulcerating de rmal lesions developed on 7/8 monkeys 2-4 weeks post-bite and persisted for 3-7 months. Monkeys also developed satellite lesions beyond the area of sa ndfly bites on the head, but not on the chest. Three rechallenged monkeys d eveloped lesions that healed faster than lesions from their primary challen ges. After infection, monkeys developed delayed type hypersensitivity (DTH) responses to a panel of Leishmania skin test antigens (LSTA) and, when tes ted by ELISA and IFA, showed significant post-infection antibody titres whi ch typically rose for similar to 170 days and then gradually receded during the next 100 days following the first challenge. After the second challeng e, antibody titres spiked higher within similar to 50 days and receded more rapidly. In contrast, four rhesus macaques of Chinese origin developed no lesions following infected sandfly bites, although they raised antibodies a nd LSTA reactions, indicating subclinical infection.