Infectivity of the Santa Lucia (El Salvador) strain of Plasmodium falciparum to different anophelines.

Anopheles freeborni mosquitoes were much more heavily infected with the Santa Lucia strain of Plasmodium falciparum from coastal El Salvador than were any of the other species tested. Of 5 strains of A. albimanus examined, the most heavily infected was the CA-109A and the least was the Melara, both of which come from coastal El Salvador. Of the exotic anophelines, the A. maculatus was infected at a slightly higher level than was the A. balabacensis. The incidence of highly infected individual mosquitoes was greatest in the Panama-Escobal strain of A. albimanus from the Republic of Panama; the incidence was lowest in the Melara strain from El Salvador. All strains of A. albimanus developed infected salivary glands, but the A. freeborni and A. maculatus mosquitoes appeared to develop infected glands more effeciently. Infection rates in A. freeborni mosquitoes were highest if mosquitoes were fed on Aotus trivirgatus monkeys between the 19th and 25th days of patent gametocytemia.     

Studies on the West African I strain of Plasmodium falciparum in Aotus trivirgatus monkeys.

The West African I strain of Plasmodium falciparum was isolated from a commercial airline pilot who had an overnight stay in Nigeria. Once established in the Aotus trivirgatus griseimembra monkey, the parasite produced high parasitemias and readily infected mosquitoes. Anopheles freeborni and An. maculatus mosquitoes transmitted the infection to additional animals. Infected salivary glands were also seen in An. culcifacies. Comparative infectivity studies indicated the most susceptible mosquito to be An. freeborni, followed by An. culicifacies, An. maculatus, and An. balabacensis balabacensis. Only 2 An. albimanus mosquitoes were infected out of 450 examined. The one A. t. trivirgatus monkey inoculated with this strain had very low levels of parasitemia.     

Comparative Studies on Dihydrofolate Reductases from Plasmodium falciparum and Aotus trivirgatus*

SYNOPSIS Dihydrofolate reductase (E.C. 1.5.1.3) from Plasmodium falciparum and from its host, the owl monkey (Aotus trivirgatus). were partially purified and characterized. The molecular weight of the parasite enzyme was estimated to be over 10 times as high as that of the host enzyme. The host enzyme had 2 pH optima whereas the parasite enzyme only one. The activity of the host enzyme was greatly stimulated by KCI and urea, while that of the parasite enzyme was inhibited at high concentrations of such chaotropic agents. Km of the parasite enzyme was significantly higher than that of the host enzyme. The parasite enzyme had much lower K_i for pyrimethamine than the host enzyme. Dihydrofolate reductases isolated from pyrimethamine-resistant and pyrimethaminesensitive strains of P. falciparum were found to be similar.     

Comparative studies on dihydrofolate reductases from Plasmodium falciparum and Aotus trivirgatus.

Dihydrofolate reductase (E.C. 1.5.1.3) from Plasmodium falciparum and from its host, the owl monkey (Aotus trivirgatus), were partially purified and characterized. The molecular weight of the parasite enzyme was estimated to be over 10 times as high as that of the host enzyme. The host enzyme had 2 pH optima whereas the parasite enzyme only one. The activity of the host enzyme was greatly stimulated by KCl and urea, while that of the parasite enzyme was inhibited at high concentrations of such chaotropic agents. Km of the parasite enzyme was significantly higher than that of the host enzyme. The parasite enzyme had much lower Ki for pyrimethamine than the host enzyme. Dihydrofolate reductases isolated from pyrimethamine-resistant and pyrimethamine sensitive strains of P. falciparum were found to be similar.     

Desferrioxamine suppresses Plasmodium falciparum in Aotus monkeys

Clinical observation has suggested that iron deficiency may be protective in malaria, and we have found that desferrioxamine (DF), an iron-specific chelating agent, inhibited Plasmodium falciparum growth in vitro. It was difficult to be confident that DF would be effective in an intact animal, however, because continuous exposure to DF was required in vitro and, in vivo, DF is rapidly excreted. Also, the in vitro effect of DF was overcome by addition of iron to the culture and in vivo there are potentially high local iron concentrations when iron is absorbed from the diet or released from reticuloendothelial cells. We now show that DF given by constant subcutaneous infusion does suppress parasitemia in P. falciparum-infected Aotus monkeys.     

Infectivity of Plasmodium simium to Aotus trivirgatus monkeys and different anophelines.

Infections of Plasmodium simium were induced in splenectomized and intact Aotus trivirgatus griseimembra monkeys by parasitized blood and by sporozoites from Anopheles freeborni mosquitoes. Eleven of 13 monkeys developed infection after sporozoite inoculation; prepatent periods ranged from 11 to 25 days (mean 15.8 days). Comparative infectivity studies indicated that An, freeborni mosquitoes were the most susceptible followed by An. stephensi, An. Balabacensis balabacensis, An. maculatus, An. quadrimaculatus, An. culicifacies, and An. albimanus. Studies with 3 pupal phenotypes of An. freeborni indicated that lines containing the green and nonstriped pupal phenotypes were more susceptible than the base colony; the striped phenotype was slightly less susceptible.     

Comparative infectivity of knobless and knobby clones of Plasmodium falciparum in splenectomized and intact Aotus trivirgatus monkeys

In two experiments, two knobless (K-) and two knob-producing (K+) clone-cultures of Plasmodium falciparum, FCR-3/Gambia strain, were injected into four Aotus trivirgatus monkeys. The parasitemia in the K(-)-infected splenectomized (S-) monkey rose to a peak of 2.1% on the 16th day, while it reached only 0.7% at the same time in the K+ infected S- animal. Passage from these animals (karyotype VI) into two intact (S+), naive monkeys of karyotype III resulted in very light infections somewhat higher with K+ than with K-. This experiment was repeated with two different clones in two other S- monkeys of karyotype III. Again, the parasitemia of the K+ infected monkey was appreciably below that of the K- monkey. Transfer of parasites into S+ animals of karyotype II resulted in very light infection and, as before, the K+ did somewhat better. About 2 months after its initial infection, the K(+)-infected S- animal from the second experiment came down with a recurrent malaria infection. Electron-microscopic observations on blood from this monkey revealed that the previously K+ parasites had become knobless (K-). Transfer of this material into an S+, naive monkey, again, gave a barely detectable infection. After splenectomy a recrudescence occurred. The results strongly indicate that K- clones of P. falciparum are more infectious to S- Aotus monkeys than K+ clones, whereas in S+ monkeys the situation is reversed.     

Studies on the Indochina I/CDC strain of Plasmodium falciparum in Colombian and Bolivian Aotus monkeys and different anophelines

The Indochina I/CDC strain of Plasmodium falciparum was isolated from a physician returning to the United States after working in the refugee camps along the Thailand-Kampuchean border. The strain was established in splenectomized Aotus monkeys from Colombia after being grown in vitro for 50 days. During the first three passages in Colombian monkeys, the parasites were not infective to Bolivian Aotus monkeys. After six intervening passages in Saimiri sciureus monkeys, the parasites produced high parasitemias in both Colombian and Bolivian Aotus, but gametocytes were no longer produced. Mosquito infections were obtained only during the first three passages in the Colombian monkeys. The most susceptible mosquito was Anopheles freeborni, followed by An. dirus, An. stephensi, An. maculatus, An. culicifacies, and, rarely, An. gambiae. Sporozoites were found in the salivary glands of the An. freeborni, An. dirus, An. stephensi, and An. maculatus.     

Effect of sequential infection with Plasmodium vivax and P. falciparum in the Aotus trivirgatus monkey.

Aotus trivirgatus monkeys with prior experience with Plasmodium vivax were inoculated with P. falciparum via the bites of infected mosquitoes. The animals with prior malaria had higher parasitemias and significantly higher levels of mosquito infectivity than monkeys with no prior P. vivax experience. Monkeys with a history of P. falciparum that were inoculated with P. vivax had essentially the same parasitemias as those with no prior malaria. However, levels of mosquito infectivity were markedly increased in those monkeys with a history of P. falciparum. The results imply that the introduction of another malaria species into a malarious area may result in higher levels of mosquito infection and more rapid establishment and distribution of that species.     

Studies on the North Korean strain of Plasmodium vivax in Aotus monkeys and different anophelines

Twenty-two Aotus monkeys of different karyotypes were infected with the North Korean strain of Plasmodium vivax. Aotus lemurinus griseimembra animals from Colombia produced higher maximum parasitemias and more readily infected mosquitoes than did Aotus monkeys from Bolivia (K-VI) or Peru (K-V and K-X). Comparative feedings indicated that the most susceptible mosquito species was Anopheles stephensi, followed by An. gambiae, An. dirus, An. freeborni, An. quadrimaculatus, An. culicifacies, and An. maculatus.     

Studies on a newly isolated strain of Plasmodium brasilianum in Aotus and Saimiri monkeys and different anophelines

A strain of Plasmodium brasilianum was isolated from an Aotus vociferans monkey from Peru. The parasite readily infected Aotus monkeys from Bolivia and Columbia and Saimiri sciureus monkeys from Peru and Bolivia. Highest level mosquito infections were obtained by feeding on the Saimiri monkeys. The most susceptible mosquito was Anopheles freeborni, followed by Anopheles dirus, Anopheles stephensi, Anopheles gambiae, Anopheles culicifacies, Anopheles maculatus and Anopheles albimanus. Anopheles quadrimaculatus were also susceptible to infection. Degenerating oocysts were observed in An. dirus mosquitoes infected with this parasite. Transmission via the bites of infected An. maculatus mosquitoes was obtained to 3 Bolivian Saimiri monkeys; prepatent periods were 27, 27, and 29 days.