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William E Collins

Publications and source records attributed to William E Collins.

At least 37 records · Page 2Linked to original sources

Potent immunogenicity of DNA vaccines encoding Plasmodium vivax transmission-blocking vaccine candidates Pvs25 and Pvs28-evaluation of homologous and heterologous antigen-delivery prime-boost strategy.

Transmission-blocking vaccines target the sexual stages of the malaria parasite and prevent further development within the mosquito vector halting the transmission of the parasite. Zygote/ookinetes are potential targets of antibodies inhibiting oocyst development in the mosquito midgut and rendering mosquitoes non-infectious. DNA vaccine constructs were developed expressing Pvs25 and Pvs28 (Plasmodium vivax zygote/ookinete surface proteins) fused at the amino terminus with tissue plasminogen activator signal peptide. Antibodies produced in mice after immunization with three doses recognized respective antigens in the parasites and in an ELISA, and these antibodies when tested in membrane feeding assay were potent blockers of P. vivax transmission. Co-immunization with Pvs25 and Pvs28 DNA vaccine constructs did not affect the antigen specific antibody responses against individual antigens, and the antibodies remained effective in blocking parasite transmission demonstrating 91-99% reduction in oocyst number in the mosquito midgut. Several combinations of homologous and heterologous antigen-delivery prime boost strategy were also evaluated and the results suggested that antibody titers and transmission-blocking activities by the three prime-boost strategies (DNA prime/DNA boost, DNA prime/protein boost, and protein prime/protein boost) were comparable with slightly better immunogenicity of heterologous antigen-delivery prime/boost as compared to DNA/DNA alone. These results demonstrate potent immunogenicity of DNA vaccines encoding Pvs25 and Pvs28 and warrant further evaluation in non-human primates.

Animals↗

Additional observations on the sporozoite transmission of Plasmodium knowlesi to monkeys.

Saimiri boliviensis monkeys were infected by the intravenous injection of 50 sporozoites of the H strain of Plasmodium knowlesi dissected from the salivary glands of Anopheles dirus mosquitoes; prepatent periods were 11, 12, 13, 13, 13, and 16 days. Sporozoites of P. knowlesi stored frozen for 7 days, 53 days, 20 mo, 7 yr and 7 mo, and 11 yr and 5 mo induced infections in Macaca mulatta monkeys with prepatent periods of 7, 6, 8, 10, and 7 days, respectively. After frozen storage for 11 yr and 5 mo, infections were induced in S. boliviensis with prepatent periods of 10-13 days.

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Rio Meta strain of Plasmodium vivax in New World monkeys and anopheline mosquitoes.

An archived strain of Plasmodium vivax, isolated from Rio Meta, northern Colombia, in 1972 was adapted to grow in splenectomized Aotus lemurinus griseimembra and A. nancymai monkeys. Anopheles freeborni, An. maculatus, An. dirus, An. culicifacies, and An. albimanus were shown to be susceptible to infection by feeding on infected monkeys. Infections were more readily obtained by feeding on A. L. griseimembra than on A. nancymai. Transmission through sporozoites was obtained in an A. l. griseimembra monkey after a prepatent period of 24 days.

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A retrospective examination of the effect of fever and microgametocyte count on mosquito infection on humans infected with Plasmodium vivax.

A retrospective examination was made of archival data collected between 1940 and 1963 on the infection of mosquitoes with the St. Elizabeth strain of Plasmodium vivax. Patients were undergoing malariatherapy for the treatment of neurosyphilis. A total of 845 lots of Anopheles quadrimaculatus mosquitoes were fed during primary infections and 76 during secondary infections. Average percentage infection during the primary infection was 56.55% versus 49.83% during the secondary infection. There appeared to be no relationship between microgametocye density, asexual parasite count, and percentage infection. However, very high fevers appear to have a significant effect on infection rates. Persons with fever > or = 105 degrees F showed the lowest rates of infectivity regardless of parasitemia; persons with moderate (101-104.8 degrees F) fever produced somewhat higher rates, and persons with no fever had the highest levels of infection at all parasitemia levels greater than 1,500/microL

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A retrospective examination of reinfection of humans with Plasmodium vivax.

A retrospective examination was made of archival data collected between 1940 and 1963 to determine the impact of reinfection of patients with Plasmodium vivax with homologous and heterologous strains of the parasite. Following reinfection of 14 patients with a homologous strain, the geometric mean maximum parasite count was reduced from 9,101/microL during the primary infection to 998/microL and the geometric mean daily parasite count for the first 20 days was reduced from 923/microL to 16/microL. Following reinfection of 22 patients with heterologous strains of P. vivax, the geometric mean maximum parasite count was 8,460/microL during the primary infection versus a secondary level of 9,196/microL and the geometric mean daily parasite count decreased from 847/microL/day to 335/microL/day. Reductions in fever episodes > or =101 degrees F and > or = 104 degrees F appeared to be a more sensitive measure of clinical immunity. Fever episodes > or =104 degrees F in patients with homologous strain reinfections decreased from 1.92 episodes per week to 0.18 compared with 1.24 to 0.57 in patients with heterologous infections. Fever episodes > or =101 degrees F decreased from 2.98 to 0.60 in the homologous strain compared with 2.08 to 1.07 for the heterologous infections. The average maximum fever temperature in the homologous group was 106 degrees F during the primary infection versus 103.4 degrees F for the secondary infection compared with 105.8 degrees F during the primary infections versus 105.6 degrees F for the secondary infection in the heterologous patients.

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Susceptibility of Anopheles farauti to infection with different species of Plasmodium.

A colony of Anopheles farauti, originally from the island of New Britain in Papua New Guinea, was tested for its receptivity to infection with different species of Plasmodium in comparison with An. freeborni and An. stephensi. This colony adapted well to feeding on monkeys and was infected with New World and Old World strains of P. vivax and P. falciparum, P. ovale, P. cynomolgi, and P. brasilianum.

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The development of exoerythrocytic stages of Plasmodium inui shortti in New World monkeys.

Attempts are being made to adapt Old World monkey malarial parasites to New World monkeys for vaccine and molecular studies. Several of these (Plasmodium cynomolgi Berok, Plasmodium fragile, and Plasmodium knowlesi) grow readily but have failed to produce infective gametocytes. Plasmodium gonderi and Plasmodium fieldi develop in the liver after sporozoite inoculation but have failed to establish infection in the erythrocyte. Anopheles dirus mosquitoes infected with Plasmodium inui shortti by feeding on infected macaques transmitted the infection to Saimiri boliviensis monkeys. Infective gametocytes were produced, and sporozoite transmission from Saimiri to Saimiri monkey was obtained. Exoerythrocytic stages have also been observed in the liver tissue of Saimiri monkeys. The availability of the complete transmission cycle provides an additional resource for immunologic and vaccine studies.

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A retrospective examination of mosquito infection on humans infected with Plasmodium falciparum.

A retrospective examination was made of archival data collected between 1940 and 1963 on the infection of mosquitoes with Plasmodium falciparum. Patients were undergoing malariatherapy for the treatment of neurosyphilis. A total of 913 lots of Anopheles quadrimaculatus and An. albimanus were fed on 173 patients. Mosquito infection continued to occur in a few patients beyond 200 days of patent parasitemia. The primary period of mosquito infection occurred during the first 20 days of gametocytemia. Of the 311 lots of mosquitoes fed during this period, 209 (67.20%) were infected, and of these, 163 had greater than 50% of the mosquitoes in the lots infected with at least one oocyst. During secondary periods of gametocytemia, 293 (78.76%) of 372 lots of mosquitoes were infected. The highest percentages of mosquitoes were infected from four days before to four days following peak gametocyte density. Mosquito infection rates were similar to those seen in studies with splenectomized Aotus monkeys experimentally infected with P. falciparum.

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A retrospective examination of anemia during infection of humans with Plasmodium vivax.

A retrospective examination was made of archival data on 98 patient episodes of infection with Plasmodium vivax occurring over a period of 4-11 weeks to document changes in hemoglobin (Hb) concentrations associated with continuing parasitemia. The mean percentage change in the Hb concentration for each of the 10 seven-day intervals was -13.4, -10.9, -4.8, 0.12, 0.94, 4.0, 0.69, 11.6, 2.4, and 8.3, respectively. An equilibrium appeared to be established between weeks 4 and 6. Decreases in Hb concentrations were greatest following the first week of parasitemia. Total restoration to preinfection levels did not occur during persistent parasitemia.

Anemia↗

Adaptation of a strain of Plasmodium falciparum from Ghana to Aotus lemurinus griseimembra, A. nancymai, and A. vociferans monkeys.

A strain of Plasmodium falciparum from Ghana was adapted to Aotus lemurinus griseimembra, A. nancymai, and A. vociferans monkeys. Gametocytes in splenectomized A. nancymai were infective to Anopheles freeborni mosquitoes. Sporozoite transmission was accomplished in two splenectomized A. nancymai with prepatent periods of 22 and 25 days. The Ghana III/CDC strain of P. falciparum is susceptible to treatment with chloroquine and mefloquine.

Adaptation, Biological↗

Immunization of Aotus monkeys with a functional domain of the Plasmodium falciparum variant antigen induces protection against a lethal parasite line.

Immunity to Plasmodium falciparum in African children has been correlated with antibodies to the P. falciparum erythrocyte membrane protein 1 (PfEMP1) variant gene family expressed on the surface of infected red cells. We immunized Aotus monkeys with a subregion of the Malayan Camp variant antigen (MCvar1) that mediates adhesion to the host receptor CD36 on the endothelial surface and present data that PfEMP1 is an important target for vaccine development. The immunization induced a high level of protection against the homologous strain. Protection correlated with the titer of agglutinating antibodies and occurred despite the expression of variant copies of the gene during recurrent waves of parasitemia. A second challenge with a different P. falciparum strain, to which there was no agglutinating activity, showed no protection but boosted the immune response to this region during the infection. The level of protection and the evidence of boosting during infection encourage further exploration of this concept for malaria vaccine development.

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Experimental infection of Anopheles farauti with different species of Plasmodium.

Studies were conducted to determine the susceptibility of Anopheles farauti to different species and strains of Plasmodium. Mosquitoes were infected by feeding on animals or cultures infected with different strains of P. vivax, P. falciparum, P. ovale, P. coatneyi, P. gonderi, P. simiovale, P. knowlesi, and P. brasilianum. Infections of P. vivax and P. coatneyi were transmitted via sporozoites from An. farauti to monkeys. Comparative infection studies indicated that An. farauti was less susceptible to infection than An. stephensi, An. gambiae, An. freeborni, and An. dirus with the Salvador I strain of P. vivax, but more susceptible than An. stephensi and An. gambiae to infection with the coindigenous Indonesian XIX strain.

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Infection of Aotus and Saimiri monkeys with Plasmodium gonderi.

Attempts were made to infect 4 species of New World monkeys (Saimiri boliviensis, Aotus nancymai, A. vociferans, A. azarae boliviensis) with Plasmodium gonderi, a malaria parasite of African monkeys. Sporozoites were obtained from Anopheles dirus or A. stephensi mosquitoes that fed on an infected rhesus monkey (Macaca mulatta). Inoculation of sporozoites was by injection of dissected sporozoites by either the intravenous or intrahepatic routes, or by mosquito bite. Liver biopsies done 7 or 8 days after sporozoite inoculation showed that hepatocytes of all 4 species of these New World monkeys supported exoerythrocytic stages of P. gonderi, but daily blood film examination during a 60-day observation period failed to detect blood stages of the parasite.

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Plasmodium vivax blood-stage dynamics.

We examine the dynamics of parasitemia and gametocytemia reflected in the preintervention charts of 221 malaria-naive U.S. neurosyphilis patients infected with the St. Elizabeth strain of Plasmodium vivax, for malariatherapy, focusing on the 109 charts for which 15 or more days of patency preceded intervention and daily records encompassed an average 98% of the duration of each infection. Our approximations of merogony cycles (via "local peaks" in parasitemia) seldom fit patterns that correspond to "textbook" tertian brood structures. Peak parasitemia was higher in trophozoite-induced infections than in sporozoite-induced ones. Relative densities of male and female gametocytes appeared to alternate, though without a discernably regular period. Successful transmission to mosquitoes did not depend on detectable gametocytemia or on absence of fever. When gametocytes were detected, transmission success depended on densities of only male gametocytes. Successful feeds occurred on average 4.7 days later in an infection than did failures. Parasitemia was lower in homologous reinfection, gametocytemia lower or absent.

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A retrospective examination of sporozoite-induced and trophozoite-induced infections with Plasmodium ovale: development of parasitologic and clinical immunity during primary infection.

A retrospective analysis was made of clinical and parasitologic parameters in patients with induced Plasmodium ovale infection to document the initial clinical and parasitologic response and their subsequent development of clinical and parasitologic immunity, and to determine the effect of previous homologous and heterologous malaria on subsequent infection with this parasite. The prepatent periods were relatively uniform. Eight patients injected with sporozoites that had been stored frozen had a median prepatent period of 14 days (range = 14-20 days). Thirty-five patients infected via the bites of infected mosquitoes had a median prepatent period of 15 days (range = 12-18 days). In eight patients previously infected with P. vivax, the median prepatent period was 16 days. High-intensity fever (> or = 104 degrees F) was frequently seen, with instances of fever > or = 106 degrees F recorded on many occasions. Fever > 101 degrees F and > 104 degrees F occurred for much shorter periods of time than had been observed in patients infected with P. falciparum. Parasite counts > 10,000/microL were infrequent; in most patients, such parasite counts rarely lasted more than two or three days. Gametocytemia was generally of low density and lasted only a few days. The overall length of the clinical and parasitologic period was much shorter compared with that seen in patients infected with P. falciparum. Previous infection with P. ovale did not prevent reinfection, but resulted in reduced levels of parasitemia and fever. Previous infection with heterologous species of Plasmodium did not prevent infection; some reduction in the frequency and intensity of fever and parasite counts was evident. Previous infection with homologous or heterologous parasites failed to eliminate the production of infective gametocytes. A total of 462 lots of mosquitoes were fed on 67 patients with no previous history of infection. Of these feedings, 168 (36.4%) resulted in infection as determined by the presence of oocysts on the midguts of dissected mosquitoes. As shown, the infection rate increased with the density of gametocytes even though 48 (23.4%) of 205 lots of mosquitoes fed when no gametocytes were detected were infected.

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Plasmodium malariae infection boosts Plasmodium falciparum gametocyte production.

We analyzed records of malaria therapy patients sequentially or simultaneously inoculated with Plasmodium falciparum and Plasmodium malariae. Gametocyte production was enhanced in P. falciparum by prior or concurrent P. malariae infection but diminished or unaffected in P. malariae by P. falciparum. Conversely, asexual-form production was diminished in P. malariae but unaffected in P. falciparum.

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