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Biomedical subjects

W E Collins

Publications and source records attributed to W E Collins.

At least 37 records · Page 2Linked to original sources
PubMed1999

Susceptibility of Panamanian Aotus lemurinus lemurinus to sporozoite-induced Plasmodium falciparum (Santa Lucia) infection.

Aotus monkeys are good models for erythrocyte-induced Plasmodium falciparum and P. vivax infections and have been extensively used in malarial drug and vaccine development. Recently, it has been shown that certain species of Aotus can be infected with sporozoites, and that the degree of susceptibility varies among species. We demonstrate here that Panamanian Aotus lemurinus lemurinus are susceptible to a sporozoite-induced infection, opening the possibility that this species of Aotus could be used as models for testing the efficacy of pre-erythrocytic P. falciparum vaccines and drug candidates directed at the pre-erythrocytic stages of P. falciparum and P. vivax malaria. In this species, we compared sporozoite infection rates. Two of four animals splenectomized prior to infection with sporozoites developed patent parasitemias. Seven of eight animals splenectomized either 7 or 35 days after infection became parasitemic. Additionally, we used a P. falciparum-specific polymerase chain reaction (PCR) method to detect the early appearance of parasitized erythrocytes in the blood prior to detection by conventional microscopy, and found that the parasitemia was detected first in five animals by the PCR method, first in three animals by blood film, with one parasitemia detected simultaneously. We also demonstrated the feasibility of infecting monkeys located in Panama with sporozoites isolated at an insectary in Atlanta, thus documenting the feasibility of similar studies where the insectary and monkey colony are not in the same location. A subsequent attempt to infect these monkeys using sporozoites was not successful, suggesting that this model of human malaria is not yet ready for routine use in vaccine or drug efficacy screening. This model merits further study because of the importance of testing pre-erythrocytic P. falciparum malaria vaccines and drugs in animals.

Animals↗
PubMed1999

Cytokine production in rhesus monkeys infected with Plasmodium coatneyi.

Plasmodium coatneyi infection in rhesus monkeys has been used as a model for studying human malaria. Cytokine production in this model, however, has so far not been examined. In this study, four rhesus monkeys were infected with P. coatneyi, with another four animals serving as uninfected controls. Blood samples were taken for the determination of daily parasitemia, and cytokine and prostaglandin E2 (PGE2) levels at days 0, 3, 5, 7, and 10. All inoculated animals became infected, with synchronized appearance of ring-stage parasites. Infected monkeys had increased plasma levels of proinflammatory cytokines (interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha) during the late stage of the infection. They also had increased production of ciliary neurotrophic factor. In conjunction with the production of proinflammatory cytokines, infected monkeys also had gradual increases in the production of PGE2. A continued definition of the P. coatneyi/rhesus monkey animal model should be useful for the elucidation of the immunopathogenesis of human malaria.

Animals↗
PubMed1999

A retrospective examination of secondary sporozoite- and trophozoite-induced infections with Plasmodium falciparum: development of parasitologic and clinical immunity following secondary infection.

A retrospective study was made of clinical records to determine parasitemia and episodes of fever of 59 patients reinfected with Plasmodium falciparum for treatment of neurosyphilis, which was considered standard medical care at the time. Records were collected at the National Institutes of Health laboratories in Columbia, South Carolina and Milledgeville, Georgia during the period 1940 to 1963. Nineteen patients were infected via the bites of Anopheles albimanus, An. quadrimaculatus, or An. freeborni mosquitoes; the median prepatent period was 11.5 days. It was evident that clinical immunity, as measured by the frequency of fever, particularly high intensity fever (> or = 104 degrees F), was increased following reinfection. The parasitologic immunity, as measured by the frequency of asexual parasite counts and gametocyte counts, was also evident. In general, in secondary infections with homologous and/or heterologous strains of P. falciparum, fever episodes > or = 101 degrees F and > or = 104 degrees F were reduced in number, parasitemia was reduced, and gametocyte production was reduced. However, despite long courses of parasitemia during their primary infections, most patients developed fever and, in some cases, high-density parasitemia and gametocytemia following reinfection. The intensity of the secondary response did not appear to be associated with the length of the previous course of parasitemia. In addition, current infection with heterologous strain parasites did not prevent the development of fever or higher density parasite counts following imposition of the new strain of parasite.

Animals↗
PubMed1999

A retrospective examination of sporozoite- and trophozoite-induced infections with Plasmodium falciparum in patients previously infected with heterologous species of Plasmodium: effect on development of parasitologic and clinical immunity.

A retrospective examination was made to determine parasitemia and episodes of fever in 97 patients, previously infected with Plasmodium malariae, P. ovale, and/or P. vivax, who were reinfected with P. falciparum for treatment of neurosyphilis, the standard treatment at the time. Data were collected at the National Institutes of Health laboratories in Columbia, South Carolina and Milledgeville, Georgia during the period 1940 to 1963. Results were compared with observations recorded for patients following primary infection with P. falciparum. The mean daily percentage of patients with fever > or = 101 degrees F during the first 20 days of primary infection with P. falciparum was 42.4; the percentage with fever > or = 104 degrees F was 19.9%. Those previously infected with P. ovale, P. vivax, and P. malariae had mean daily percentages of fever > or = 101 degrees F and > or = 104 degrees F of 39.1% and 14.8%, 39.1% and 19.4%, and 28.4%, and 11.3%, respectively. Previous infection with P. ovale or P. vivax had little, if any, effect on subsequent clinical malaria due to P. falciparum, whereas infection with P. malariae resulted in reduced frequencies of fever. A similar comparison was made for parasite counts > or = 1,000/microl and > 10,000/microl. The percentages for 268 patients during the first 20 days of primary infection with P. falciparum parasite counts > or = 1,000/microl and > or = 10,000/microl were 58.2% and 29.9%, respectively. Those previously infected with P. ovale, P. vivax, and P. malariae had mean daily percentages of parasitemia > or = 1,000/microl and > or = 10,000/microl of 58.0% and 24.3%, 57.3% and 31.1%, and 45.9% and 19.0%, respectively. Previous infection with P. malariae resulted in a reduction in the frequency of high-density parasitemia (> or = 10,000/microl) as well as an asexual parasite count > or = 1,000/microl. These results suggest that P. falciparum and P. malariae share common antigens that are able to induce parasitologic and clinical protection when infection with P. falciparum follows that with P. malariae. The results did not suggest that protection to P. falciparum is provided by previous infection with P. ovale or P. vivax.

Animals↗
PubMed1999

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

A retrospective analysis was made of the parasitologic and fever records of 318 patients who had been infected with the El Limon, Santee Cooper, or McLendon strains of Plasmodium falciparum for treatment of neurosyphilis between 1940 and 1963 to determine the development of parasitologic and clinical immunity during primary infection. The presence of fever > or = 101 degrees F and > or = 104 degrees F, asexual parasite counts > or = 1,000 and > or = 10,000/microl, and gametocyte counts > or = 100/microl and > or = 1,000/microl are presented. The frequency of fever (number of patients with fever/number of patients remaining in study) for the first 100 days of patent parasitemia, the frequency of parasite counts > or = 1,000 and > or = 10,000/microl during the first 100 days of patent parasitemia, and the frequency of gametocyte counts > or = 100 and > or = 1,000/microl during the first 100 days of patent parasitemia are presented for 4 groups of patients: 1) sporozoite-induced and 2) trophozoite-induced infections requiring treatment during their primary attack, and 3) sporozoite-induced and 4) trophozoite-induced infections not requiring treatment during the primary attack. For each sporozoite-induced infection, the route of inoculation (bites or syringe), the species of mosquito used, the number of mosquito glands or bites, the intensity of salivary gland infection, and the length of the prepatent period are recorded. Prepatent periods for 109 sporozoite-induced infections ranged from 6 to 28 days. Patients with parasitologic or clinical findings that required suppressive, but non-curative treatment, during the primary attack had higher frequency of fever, parasitemia, and gametocytemia than patients not so treated. Fever was concentrated in the first 2 weeks of patent parasitemia although instances of fever were reported >100 days after infection. High-density parasitemia was also concentrated early in the infection; instances of parasite counts > or = 10,000/microl occurred > 75 days after infection. In conclusion, immunity to infection with P. falciparum was shown to develop rapidly. Following primary infection, clinical and parasitologic immunity was evident within 2-3 weeks following the detection of parasites in the peripheral circulation.

Animals↗
PubMed1999

A retrospective examination of the patterns of recrudescence in patients infected with Plasmodium falciparum.

A retrospective examination was made to determine median intervals between recrudescences of Plasmodium falciparum in 343 neurosyphilitic patients who were given malariatherapy, which was routine care at that time. Data were collected at the National Institutes of Health laboratories in Columbia, South Carolina and Milledgeville, Georgia during the period 1940 to 1963. The geometric mean days of peak parasite count for the patients were 8, 26.5, 43.5, 62, 78.5, and 95.5 days, respectively. The intervals between these peaks of 18.5, 17, 18.5, 16.5, and 17 days suggest a fixed time frame for the appearance of different dominant parasite populations during the first 100 days of patent infection. When the data from these same patients were examined for mean peak parasite counts, the patterns indicated a consistent decrease in parasite count suggestive of increasing immunity, which was sufficient to reduce but not eliminate subsequent parasite populations. The geometric mean peak parasite counts for the 343 patients during the primary attack and the first 5 recrudescences were 40,350, 6,975, 5,090, 3,820, 3,455, and 2,375/microl, respectively.

Animals↗
PubMed1999

Studies on infections with the Berok strain of Plasmodium cynomolgi in monkeys and mosquitoes.

Infections with the Berok strain of Plasmodium cynomolgi were induced in Macaca mulatta, Macaca fascicularis, Macaca nemestrina, Aotus lemurinus griseimembra, Aotus azarae boliviensis, and Saimiri boliviensis monkeys. Transmission was obtained with sporozoites developing in Anopheles peditaeniatus, Anopheles maculatus, Anopheles quadrimaculatus, Anopheles culicifacies, and Anopheles dirus mosquitoes. This strain of P. cynomolgi offers significant potential for a number of experimental studies. The parasite induces high-density parasite counts in both Old World and New World monkeys; rhesus monkeys readily support the development of gametocytes infectious to different anopheline mosquitoes routinely maintained in the laboratory; the gametocytes are infective to laboratory-maintained Anopheles albimanus, a vector rarely susceptible to plasmodia of Old World monkeys; encapsulated oocysts are produced in An. culicifacies as well as in Anopheles gambiae; and the parasite has been adapted to long-term in vitro culture.

Animals↗
PubMed1999

A historical review of the F-1 strain of Anopheles freeborni as a host and vector for studies of malaria.

A review was made of the use of a specific strain of Anopheles freeborni from California (F-1) that has been used extensively in experimental investigations of malaria for more than 50 years. The F-1 strain of An. freeborni has been shown to be a suitable experimental host and vector for different species of Plasmodium that cause malaria in humans and nonhuman primates for biologic, immunologic, and chemotherapeutic studies. Eleven species of Plasmodium fully completed sporogonic development; development of sporozoites within mature oocysts occurred in an additional 7 species. Transmission through An. freeborni from human to human, monkey to human, or monkey to monkey has been demonstrated for 9 species of Plasmodium.

Animals↗
PubMed1999

Adaptation of the AMRU-1 strain of Plasmodium vivax to Aotus and Saimiri monkeys and to four species of anopheline mosquitoes.

A chloroquine-resistant strain of Plasmodium vivax (AMRU-1) from Papua New Guinea has been adapted to grow in 4 species of Aotus monkeys (Aotus lemurinus griseimembra, Aotus vaciferans, Aotus nancymai, and Aotus azarae boliviensis), hybrid Aotus monkeys, and Saimiri boliviensis monkeys. Whereas it was possible to infect Saimiri monkeys with this parasite by inoculation of parasitized erythrocytes, only 42% of Saimiri monkeys became infected, compared to 92% of Aotus monkeys attempted. Comparative mosquito feedings showed that only A. vociferans, A. l. griseimembra, and Saimiri boliviensis monkeys produced infections in mosquitoes. Oocysts were observed on the guts of the 4 species of mosquitoes used (Anopheles gambiae, Anopheles stephensi, Anopheles freeborni, and Anopheles dirus), but sporozoite transmission was effected only with the intravenous inoculation of sporozoites from An. dirus into an A. l. griseimembra monkey.

Adaptation, Biological↗
PubMed1998

The evolution of primate malaria parasites based on the gene encoding cytochrome b from the linear mitochondrial genome.

We report a phylogenetic analysis of primate malaria parasites based on the gene encoding the cytochrome b protein from the mitochondrial genome. We have studied 17 species of Plasmodium, including 14 parasitic in primates. In our analysis, four species were used for rooting the Plasmodium phylogenetic tree: two from closely related genera (Hepatocystis sp. and Haemoproteus columbae) and two other Apicomplexa (Toxoplasma gondii and Theileria parva). We found that primate malaria parasites form a monophyletic group, with the only exception being the Plasmodium falciparum-Plasmodium reichenowi lineage. Phylogenetic analyses that include two species of non-Plasmodium Haemosporina suggest that the genus Plasmodium is polyphyletic. We conclude that the biologic traits, such as periodicity and the capacity to relapse, have limited value for assessing the phylogenetic relationships among Plasmodium species. For instance, we found no evidence that would link virulence with the age of the host-parasite association. Our studies also reveal that the primate malaria parasites originated in Africa, which contradicts the presently held opinion of Southeast Asia as their center of origin. We propose that the radiation of Asian monkey parasites is a recent event where several life history traits, like differences in periodicity, appeared de novo.

Animals↗
PubMed1998

Salvador II strain of Plasmodium vivax in Aotus monkeys and mosquitoes for transmission-blocking vaccine trials.

Infections with the Salvador II strain of Plasmodium vivax in Aotus lemurinus griseimambra monkeys were fed upon by Anopheles freeborni mosquitoes. Periods of mosquito infectivity were determined to establish a model system for the testing of transmission-blocking vaccines. The highest levels of mosquito infection were associated with the ascending asexual parasitemia after reaching 1,000/microl, and before the peak asexual parasite count. Sporozoite-induced infections were more infectious than were trophozoite-induced infections. Secondary episodes of parasitemia were also infectious, indicating the lack of development of naturally developing transmission-blocking immunity to this strain of P. vivax in splenectomized Aotus monkeys following single infections.

Animals↗
PubMed1998

Attempts to transmit the N-3 strain of Plasmodium fieldi to Aotus monkeys.

Aotus lemurinus griseimembra monkeys inoculated with parasitized erythrocytes of the N-3 strain of Plasmodiumfieldi had transient low-density parasitemia. Exoerythrocytic stages of this strain of parasite were demonstrated in sections of liver from Aotus vociferans monkeys taken 8 days after the intravenous inoculation of sporozoites dissected from the salivary glands of Anopheles dirus mosquitoes; no blood-stage infections were observed.

Animals↗
PubMed1998

Plasmodium inui is not closely related to other quartan Plasmodium species.

Plasmodium inui (Halberstaedter and von Prowazek, 1907), a malarial parasite of Old World monkeys that occurs in isolated pockets throughout the Celebes, Indonesia, Malaysia, and the Philippines, has traditionally been considered to be related more closely to Plasmodium malariae of humans (and its primate counterpart Plasmodium brasilianum), than to other primate Plasmodium species. This inference was made in part because of the similarities in the periodicities or duration of the asexual cycle in the blood, the extended sporogonic cycle, and the longer period of time for development of the pre-erythrocytic stages in the liver. Both P. inui and P. malariae have quartan (72 hr) periodicities associated with their asexual cycle, whereas other primate malarias, such as Plasmodium fragile and Plasmodium cynomolgi, are associated with tertian periodicities (48 hr), and Plasmodiumn knowlesi, with a quotidian (24 hr) periodicity. Phylogenetic analyses of portions of orthologous small subunit ribosomal genes reveal that P. inui is actually more closely related to the Plasmodium species of the "vivax-type" lineage than to P. malariae. Ribosomal sequence analysis of many different, geographically isolated, antigenically distinct P. inui isolates reveals that the isolates are nearly identical in sequence and thus members of the same species.

Animals↗
PubMed1998

Studies on infections with two strains of Plasmodium inui from Taiwan in rhesus monkeys and different anopheline mosquitoes.

Rhesus monkeys infected with the Taiwan strains of Plasmodium inui could be appropriate models for understanding host-parasite relationships during long-term chronic infection. Two strains of P. inui originally from Taiwan were studied in rhesus monkeys and different anopheline mosquitoes. Maximum parasite counts for 13 intact animals infected with the Taiwan I strain ranged from 22,215 to 760,000/microl (median maximum parasite count = 242,800/microl). Following splenectomy, the maximum parasite count for the 9 animals ranged from 160,000 to 2,360,000/microl (median = 1,160,000/microl). Sporozoite transmission was demonstrated via the bites of infected Anopheles dirus mosquitoes and by the intravenous inoculation of sporozoites harvested from the guts of infected Anopheles maculatus. Prepatent periods were 12 and 20 days, respectively. With monkeys infected with the Taiwan II strain, the parasite counts when intact were from 40,882 to 223,686/microl. After splenectomy, maximum parasite counts ranged from 96,750 to 1,960,000/microl (median maximum parasite count for 8 splenectomized animals = 840,000/microl). Two transmissions were obtained via the bites of infected An. dirus mosquitoes; prepatent periods were 10 days. Limited studies with progressively increasing doses of pyrimethamine resulted in parasites more resistant to treatment.

Animals↗
PubMed1998

Adaptation of a strain of Plasmodium vivax from Mauritania to New World monkeys and anopheline mosquitoes.

A strain of Plasmodium vivax from Mauritania was adapted to develop in Aotus lemurinus griseimembra, Aotus nancymai, Saimiri boliviensis, and hybrid Aotus monkeys. Infections were induced via the inoculation of sporozoites dissected from the salivary glands of Anopheles gambiae, Anopheles freeborni, and Anopheles stephensi mosquitoes or the intravenous passage of infected erythrocytes. Infections in 3 A. lemurinus griseimembra monkeys readily infected mosquitoes. Four lines of the Mauritania parasites have been stored frozen for further reference.

Adaptation, Physiological↗
PubMed1997

Induction of protective antibodies in Saimiri monkeys by immunization with a multiple antigen construct (MAC) containing the Plasmodium vivax circumsporozoite protein repeat region and a universal T helper epitope of tetanus toxin.

Previous attempts in inducing protective immunity against Plasmodium vivax in human volunteers and nonhuman primates with recombinant circumsporozoite (CS) proteins have been unsuccessful, largely due to the failure of generating antibodies against the protective B epitope AGDR in the CS protein repeat region. We report here an immunization study in Saimiri monkeys with a multiple antigen construct (MAC) containing the P. vivax CS protein repeat region and a T helper epitope of tetanus toxin formulated in different adjuvants. Monkeys immunized three times with MAC in copolymer P1005, copolymer P1005 plus RaLPS, or MF-75 had titers of antibodies against CS repeat, sporozoites and the protective B epitope AGDR significantly higher than those immunized with MAC in alum or PBS (P < 0.05). Antibody levels in animals that received P1005 were maintained at high level for 7 months after the last immunization. Upon challenge with 10000 sporozoites 2 weeks after the last immunization, 75% (three of four) of monkeys from the alum group, 50% (three of six) of monkeys from the P1005 plus RaLPS group, 40% (two of five) of monkeys from the P1005 group, 33% (two of six) of monkeys from the MF-75 group, and 17% (one of six) of monkeys from the MAC alone group were fully protected. When immunized animals were challenged again with 30000 sporozoites 22 weeks after the last immunization. 40% (two of five) monkeys from the P1005 group were fully protected. The remaining (three) in this group developed low parasitemia (< 2000 parasites mm-3 of blood) after significantly longer prepatent period (P < 0.05). In addition, 17% (one of six) of monkeys each from the P1005 plus RaLPS and MF-75 groups were also fully protected. Protected animals had higher levels of prechallenge anti-AGDR antibody titers than unprotected (1933 vs 281 for the first challenge, P > 0.05; 21527 vs 196 for the rechallenge, P < 0.05). Anti-AGDR antibody titers were positively correlated with the prepatent period of infected animals (r = 0.42 for the first challenge, P > 0.05; r = 0.60 for the rechallenge, P < 0.05) and negatively correlated with the peak parasitemia (r = -0.39 for the first challenge, P < 0.05; r = 0.50 for the rechallenge, P < 0.05). The results suggested that when combined with the use of potent adjuvants and T helper epitopes, MAC subunit vaccines may potentially offer protection against malaria infection.

Amino Acid Sequence↗
PubMed1997

Protective immunity induced in squirrel monkeys with a multiple antigen construct against the circumsporozoite protein of Plasmodium vivax.

Saimiri boliviensis monkeys were immunized with a multiple antigen construct [(PvCS)2]2(P2)2 directed against the circumsporozoite protein of Plasmodium vivax or a combination of the multiple antigen construct with nonionic copolymer P1005, with P1005 and lipopolysaccharide, with muramyl tripeptide Mf-75, or with alum. Following intravenous challenge with 10,000 sporozoites of the Salvador I strain of P. vivax, 11 of the 26 monkeys were protected against patent parasitemia. Ten additional animals were partially protected. Following rechallenge of the 26 monkeys with 30,000 sporozoites of the homologous strain of parasite, four monkeys were totally protected and nine animals were partially protected.

Adjuvants, Immunologic↗