Forty-three homozygous albino hairless mice (Mus musculus) were inoculated intradermally on the head, back, sides and base of the tail with suspensions of lepromatous tissue containing numerous Mycobacterium lepraemurium (Hawaiian strain). Visible nodules were noted in all mice. These lepromatous nodules enlarged slowly and often merged with each other, covering up to two thirds of the dorsum. Several mice became blind during the course of the infection. All of the mice died or were killed 68 to 287 days following inoculation. Post-mortem examinations on representative mice showed, in addition to observed cutaneous lesions, generalized systemic murine leprosy. Smears and histological sections from nodules, skin, lymph nodes, spleen, liver, kidney, heart and lung were positive for acid-fast bacilli. The cysts in the skin (which are degenerated hair follicles filled with keratin-like material and which are one of the characteristics of hairless mice) contained scattered acid-fast bacilli, but no acid-fast globi. Ten mice with hair (M. musculus) which were used as controls did not reveal noticeable cutaneous nodules; however, all developed generalized visceral leprosy similar to that of the hairless M. musculus. Thus, hairless mice (with thymus) can be looked upon as a model for studying experimental cutaneous leprosy.

Cutaneous leishmaniasis was produced in 90 hairless mice, Mus musculus , with cultures of two strains of Leishmania tropica (one isolated from an exogenous human case in Texas, and the other a gerbil strain from the USSR). The mice were inoculated intradermally in five areas of the dorsal side of the body. Most of the inoculated mice developed visible cutaneous leishmaniasis. The early lesions at the sites of inoculation were small red papules appearing within one to two months following inoculation; some of these papules disappeared after a few weeks, others became nodular or pustular. These lesions gradually enlarged and became ulcerated, measuring about 5 to 10 mm in diameter, and some persisted as long as 386 days. The edges of the lesions were usually raised, indurated, and pink; the adjacent skin showed no visible reaction. The centre of the ulcer was either moist or covered with a dry brownish-grey crust. In a few cases the lesions were very extensive and merged with each other, covering nearly two thirds of the dorsal body surface. Smears from the edges of the lesions were positive for the amastigote (aflagellar) form of L. tropica , which produced infections when inoculated into other hairless mice and grew readily in promastigote (flagellar) form on NNP-2 medium ( Packchanian , 1959 ) with suitable antibiotics ( Packchanian , 1957 ). Although mice were inoculated intradermally with L. tropica , several animals with extensive skin lesions of cutaneous leishmaniasis also developed generalized leishmaniasis. This was proved by positive blood culture tests for promastigotes (from 15 mice) and by demonstration of the amastigote form of L. tropica in various organs such as the spleen, liver, kidney, heart and lymph nodes. On the other hand, heart blood from 18 mice with small skin lesions when tested during 62 to 269 days following infection, yielded negative results for promastigotes. The mice were kept under observation (60 to 478 days) before they were killed or died. The results of this study have demonstrated that the hairless mouse, Mus musculus , is a suitable laboratory animal for studying experimental cutaneous leishmaniasis.

: Experimental Trypanosoma gambiense infection in 19 species and subspecies of rodents was investigated with special reference to the susceptibility or resistance of each species of rodent to a virulent strain of T. gambiense. Eight species and subspecies of rodents contracted acute trypanosomiasis and died within a week. In seven species and subspecies of rodents, T. gambiense infection ran a subacute to chronic course. The control animals, Mus musculus and Rattus norvegicus, contracted acute infection and died by trypanosomiasis within a week. Laboratory stock of T. gambiense (BW-NIH-UT strain), after being maintained over nine years in P. m. gambeli by syringe passage, has not lost its original virulence and pathogenicity to susceptible test animals. P. m. gambeli (albino, colored and hairless) is recommended for maintaining laboratory stock of T. gambiense as a timesaving and safe procedure. The possibility of certain species of American rodents becoming reservoir hosts for pathogenic African trypanosomes and the danger of introducing ruminants infected with trypanosomiasis from Africa to America, Asia and Europe where mechanical transmission of the disease from them to indigenous mammals by blood-sucking insects, vampire bat, etc., may take place is discussed.

1.(1) Acute, always fata, Trypanosoma gambiense and Trypanosoma rhodesiense infections in mice (Mus musculus) were cured with adequate dosages of captostibone [sodium 2-(carboxy-methylmercapto) benzene stibonate].2.(2) Administration of 150 to 200 mg./kg. of captostibone sodium daily for 4 days intraperitoneally produced from 80 to 100 per cent. curative effects in mice infected with T. gambiense or T. rhodesiense; with dosages ranging from 75 to 125 mg./kg. daily for 4 days, percentages of cures were less.3.(3) All mice that survived and remained free of trypanosomes were discarded as cured 60 to 212 days following cessation of therapy.4.(4) One hundred and fifty-five untreated control mice, 70 infected with T. gambiense and 85 infected with T. rhodesiense, all invariably died of acute trypanosomiasis in from 3 to 5 days.

SummaryAdministration of single doses of nitrofurazone of 50 to 150 mg./kg. I.M. to 32 guinea pigs each infected with one of 11 different strains of T. gambiense cured half the infections and suppressed the rest. The effectiveness of a given dose of nitrofurazone varied with the strain of T. gambiense; infections caused by some strains (E, K, X, or Z) were cured, while infections caused by other strains (M, Q, R, T, U, and Y) were only suppressed. Variable therapeutic results were obtained with infections caused by strain L. Nitrofurazone produced a better therapeutic response in guinea pigs infected with T. gambiense when the drug was administered about a month following the infection than when treatment was initiated three to five months following infection.Single doses of nitrofurazone were apparently not so effective in subacute T. rhodesiense infections as in chronic T. gambiense infections in guinea pigs. Single doses of nitrofurazone, 50 to 150 mg./kg. I.M., administered to 30 guinea pigs each infected with one of seven different strains of T. rhodesiense were curative in 10 per cent, suppressive in 80 per cent and ineffective in 10 per cent of the animals.

SummaryNitrofurazone, 5-nitro-2-furaldehyde semicarbazone (Furacin), a new trypanocidal drug, was used for the first time on human beings in the treatment of 32 patients suffering with Trypanosoma gambiense sleeping sickness, with encouraging therapeutic results. Administered orally, the drug is readily absorbed from the intestinal tract and is effective against trypanosomes in the circulating blood and in the cerebrospinal fluid. Oral doses of 2.1 to 12.5 mg./kg. t.i.d. for seven to thirty-six days were tolerated by the patients without any permanent ill effects. During therapy some cases experienced side effects of temporary nausea and vomiting, and muscular and articular pains in the legs, which subsided within a month following cessation of therapy.Cures were effected with nitrofurazone alone in 2 of 3 adults without central nervous system involvement; 2 of 3 children with serious C.N.S. involvement were cured with a combination of nitrofurazone and Lomidine. A so-called "cocktail treatment" of nitrofurazone in conjunction with Bayer 205, Lomidine and Arsobal produced favorable prognoses in 9 of 20 hopeless relapsing cases refractory to all previous treatment. This combination was no more toxic than any of the drugs taken separately.In treating African sleeping sickness, particularly chronic, drug-resistant cases with severe nervous involvement, it is recommended that nitrofurazone be used orally, either alone or in conjunction with other trypanocides.

"Chemotherapy of African Sleeping Sickness. I. Chemotherapy of Experimental Trypanosoma Gambiense Infection in Mice (Mus Musculus) with Nitrofurazone" published on Jul 1955 by The American Society of Tropical Medicine and Hygiene.

Journal Article Altitude Tolerance of Normal and Infected Insects Get access Ardzroony Packchanian Ardzroony Packchanian School of Medicine, The University of Texas, Galveston Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Economic Entomology, Volume 47, Issue 2, 1 April 1954, Pages 230–238, https://doi.org/10.1093/jee/47.2.230 Published: 01 April 1954