The study was conducted in compliance with the US Animal Welfare Act and Philippine Association for Laboratory Animal Science (PALAS) guidelines, and it adhered to principles stated in the National Research Council publication. Twenty-four captive-bred, healthy male and female Philippine cynomolgus monkeys (exposure, were used. of leprosy at several sites. Overall, however, cynomolgus monkeys seem minimally susceptible to leprosy after experimental administration. Introduction Leprosy, caused by and develops cutaneous and visceral lesions Smoc2 of lepromatous leprosy in naturally acquired leprosy or after experimental administration of and serves as a model of human disease. Cynomolgus monkeys also seem somewhat susceptible to inoculation is unknown. A report published in 1941 vaguely describes experimental inoculation of one cynomolgus monkey, and there is one report of naturally acquired borderline lepromatous leprosy in a captive Philippine cynomolgus monkey.15,16 Here, as a first step to developing a practical non-human primate model of human leprosy, we experimentally administered to groups of cynomolgus monkeys and monitored them for signs of leprosy. Methods Protocol and animals. The animal use protocol for this work was approved by the Leonard Wood Memorial Institutional Animal Care and Use Committee. The study was conducted in compliance with the US Animal Welfare Act and Philippine Association for Laboratory Animal Science (PALAS) guidelines, and it adhered to principles stated in the National Research Council publication. Twenty-four captive-bred, healthy male and female Philippine cynomolgus monkeys (exposure, were used. The latter included nasal smears for acid fast bacilli (AFB) and antiCphenolic glycolipid-1 (PGL-1) immunoglobulin M (IgM) and IgG antibody levels. For all procedures, monkeys were anesthetized with ketamine hydrochloride (20 mg/kg). No paralytics were used. Experimental groups and inocula. Table 1 summarizes seven experimental groups of cynomolgus monkeys and the characteristics and sources of the inocula administered. Some studies suggest that of non-human L-Glutamic acid monosodium salt primate origin may be more pathogenic.5,17 We sourced L-Glutamic acid monosodium salt three mangabey monkeys (M 1C3) with leprosy for inocula, and two of them were also simian immunodeficiency virus serology positive [SIV(+)]. We did not determine SIV serology status for any of the cynomlogus monkeys, including those monkeys inoculated with obtained from SIV(+) mangabey L-Glutamic acid monosodium salt monkeys with leprosy. For inocula obtained from patients with untreated lepromatous leprosy, samples were injected into mouse footpads to assess viability.18 Table 1 Characteristics of experimentally administered to cynomolgus monkeys by group inocula sourcesource was armadillo) to cynomolgus monkeys 3 and 4. Rationale was to assess an alternative source.8.2 108Not done1.4C2.1 1091Second administration: time 0 + 4 years. From mangabey monkey 1 SIV(C) (original source was human) to cynomolgus monkeys 2, 5, and 6. Rationale was L-Glutamic acid monosodium salt to assess an alternative source.1.2 109Not done2.5C3.1 1092From three patients with untreated lepromatous leprosy.6.5 10811/11 (100%)1.7C1.9 1093From mangabey monkey 2 SIV(+).7.9 108Not done1.8 1094From mangabey monkey 3 SIV(+).8.2 108Not doneIV + ID: 1.9 109; IN: 8.2 1085From two subjects with untreated lepromatous leprosy.3.6 1065/10 (50%)6.1C7.2 1066From two subjects with untreated lepromatous leprosy.2.1 10814/15 (93%)6.3 1087From three subjects with untreated lepromatous leprosy.3.6 10633/35 (94%)1.1 107 Open in a separate window AFB = acid fast bacilli; ID = intradermal; IN = intranasal; IV = intravenous; SIV = simian immunodeficiency virus. inocula for administration to cynomolgus monkeys were suspended in sterile phosphate-buffered saline, counted, assessed for morphological index (most), and then administered intranasally (IN) to both nostrils or as combined intravenous (IV) and intradermal (ID) inoculations, the latter to one or more adjacent sites on the ear rims, nose tip, upper lip, left lateral arm, and left lateral leg. IV inoculations were in the left saphenous vein near the calf. The concentration of in inocula of human origin ranged from 3.6 106 to 6.5 108 AFB/mL, and the concentration of in inocula of mangabey monkey origin ranged from 7.9 108 to 1 1.2 109 AFB/mL. ID and IV inoculation volumes ranged from 0.1 to 1 1 mL. All inoculations were done with a 1-mL syringe fitted with a 27-gauge needle. Clinical observations. Inoculation sites were observed monthly for the first year and then every 3C6 months until study completion. Photographs were taken to document lesion status. For 5 years after experimental administration, monkeys were observed weekly for changes in behavior, including appetite, and monitored for signs of pain, discomfort, neuritis, reversal reaction, and erythema nodosum leprosum (ENL). Histopathology. Punch skin biopsies were obtained from ID inoculation site lesions from five monkeys between 1 and 5 months after inoculation and three monkeys between.