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PubMed1975

The indirect hemagglutination test for malaria. Evaluation of antigens prepared from Plasmodium falciparum and Plasmodium vivax.

Soluble antigens were prepared from Plasmodium falciparum and P. vivax and were evaluated in the indirect hemagglutination test. These antigens, attached to aldehyde-fixed type "O" erythrocytes, detected antibodies in more than 91% of infections with the homologous Plasmodium species. Detection rates in infections caused by the heterologous species ranged from 72% to 76%. Positive reactions occurred in less than 2% of sera from persons without malaria infection.

Animals↗
PubMed1978

Plasmodium falciparum and Plasmodium vivax infections in the owl monkey (Aotus trivirgatus). I. The courses of untreated infections.

This study, the first of three designed to determine the feasibility of using owl monkeys infected with human plasmodia in the search for new, more broadly active antimalarial drugs, dealt with the characteristics of untreated infections with eight strains of Plasmodium falciparum and two strains of P. vivax. Such infections, induced by standardized inocula of these strains in 1,733 monkeys, all Aotus trivirgatus griseimembra, were followed from day of inoculation to death of self-cure. The virulence of the various strains differed strikingly. Incidences of fatal reactions, ranging from 24.4--89.4% and 8.1--45.8%, respectively, in infections with strains of P. falciparum and P. vivax, were closely related to the rate at which parasitemia evolved, the height of parasitemia in the primary attack, and/or the time period over which a high parasite level was sustained. Antemortem symptom complexes and gross tissue and organ reactions in infections with P. falciparum varied with survival time, but within that boundary, were the same for infections with all eight strains of this plasmodium. Morbidity in both fatal and self-limited infections with both plasmodial species was related to height of parasitemia; however, at comparable parasite levels, symptoms exhibited in infections with P. vivax were more severe than in infections with P. falciparum. Overall, the characteristics of infections with these plasmodia in owl monkeys were remarkably similar to those of human infections. With respect to biological features, infections with P. falciparum and P. vivax in this simian host appear to have much to offer in the search for new antimalarial drugs.

Animals↗
PubMed1986

Concentration of Plasmodium ovale- and Plasmodium vivax-infected erythrocytes from nonhuman primate blood using Percoll gradients.

Plasmodium vivax and Plasmodium ovale schizont-infected erythrocytes were separated from peripheral blood by centrifugation using discontinuous Percoll (colloidal silica) gradients. Infected Aotus monkey or chimpanzee blood was diluted and placed on a discontinuous gradient containing 30%, 40%, 45%, and 50% Percoll (v/v in media) layers before centrifugation at 1,450 X g. Parasitized erythrocytes were concentrated to greater than 95% schizont-infected cells in two bands that contained an average of one leukocyte per 500 infected cells. Mononuclear cells and trophozoites were isolated in another band and noninfected red cells, ring-infected cells, and granulocytes were pelleted to the bottom. The yield of parasitized erythrocytes ranged from 50% to close to 100% of the estimated number of infected cells in the original whole blood. Use of this Percoll procedure results in a high yield of concentrated parasitized erythrocytes and separation of these cells from host white blood cells.

Animals↗
PubMed1996

Detection of Plasmodium vivax and Plasmodium falciparum circumsporozoite antigen in anopheline mosquitoes collected in southern Thailand.

During a 13-month study on the ecology of malaria vectors in five villages in southern Thailand, Anopheles specimens collected on human-bait, bovid-bait, and in light traps were tested for the presence of Plasmodium vivax and P. falciparum circumsporozoite antigen by enzyme-linked immunosorbent assay. Plasmodium vivax antigen was detected in seven specimens and P. falciparum in 21 specimens, together representing 0.4% of the 7,938 specimens tested. In one village, Palao-U, circumsporozoite antigen was detected in 16 (0.7%) of the 2,196 specimens tested. In this village, combined rates of infection with P. falciparum and P. vivax were 0.6% for An. minimus, 1.1% for An. sawadwongporni, and 1.5% for An. maculatus. Circumsporozoite antigen was also detected in An. dirus, An. nivipes, An. barbirostris group, and An. hyrcanus group specimens. Combined P. falciparum and P. vivax entomologic inoculation rates in the wet season (March-October) were 0.05 for An. minimus, An. maculatus, and An. dirus, but 0 for An. sawadwongporni. Rates were higher in the dry season (November-February): 0.26 for An. minimus, 0.13 for An. maculatus, 0.13 for An. sawadwongporni, and 0 for An. dirus. The vectorial capacity, calculated based on human biting rate and rate of survival, of An. minimus during the dry season was more than two-fold higher than that of An. maculatus, the species with the second highest vectorial capacity.

Animals↗
PubMed1999

Blood-stage dynamics and clinical implications of mixed Plasmodium vivax-Plasmodium falciparum infections.

We present a mathematical model of the blood-stage dynamics of mixed Plasmodium vivax-Plasmodium falciparum malaria infections in humans. The model reproduces features of such infections found in nature and suggests several phenomena that may merit clinical attention, including the potential recrudescence of a long-standing, low-level P. falciparum infection following a P. vivax infection or relapse and the capacity of an existing P. vivax infection to reduce the peak parasitemia of a P. falciparum superinfection. We simulate the administration of antimalarial drugs, and illustrate some potential complications in treating mixed-species malaria infections. Notably, our model indicates that when a mixed-species infection is misdiagnosed as a single-species P. vivax infection, treatment for P. vivax can lead to a surge in P. falciparum parasitemia.

Animals↗
PubMedDate not supplied

Chloroquine/doxycycline combination versus chloroquine alone, and doxycycline alone for the treatment of Plasmodium falciparum and Plasmodium vivax malaria in northeastern Irian Jaya, Indonesia.

Combination therapy is one method of overcoming the global challenge of drug-resistant Plasmodium falciparum malaria. We conducted a hospital-based 28-day in vivo test comparing chloroquine/doxycycline to chloroquine or doxycycline alone for treating P. falciparum and Plasmodium vivax malaria in Irian Jaya, Indonesia. Eighty-nine patients with uncomplicated falciparum malaria were randomized to standard dose chloroquine (n = 30), doxycycline (100 mg every 12 hours [7 days], n = 20), or chloroquine with doxycycline (n = 39); corresponding numbers for vivax malaria (n = 63) were 23, 16, 24. Endpoints were parasite sensitivity (S) or resistance (RI/RII/RIII). Of the 105 evaluable patients, chloroquine/doxycycline cured (S) 20/22 (90.9% [95% CI 78.9-100%]) patients with P. falciparum malaria; 2/22 (9.1% [0-21%]) were RIII resistant. Doxycycline cured 11/17 (64.7% [42.0-87.4%]) patients, and chloroquine 4/20 (20% [2.5-37.5%]). Against P. vivax, chloroquine/doxycycline cured (S) 12/17 (70.6% [48.9-92.2%]) patients, doxycycline 4/12 (33.3% [6.6-59.9%]), and chloroquine 5/17 (29.4% [7.7-51.1%]). Chloroquine/doxycycline was effective against P. falciparum but only modestly effective against P. vivax. These findings support the use of chloroquine/doxycycline as an inexpensive alternative to mefloquine for treating chloroquine-resistant P. falciparum but not chloroquine-resistant P. vivax in this setting.

Adult↗
PubMed2002

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.

Animals↗
PubMed2002

The population structure of Plasmodium falciparum and Plasmodium vivax during an epidemic of malaria in the Eastern Highlands of Papua New Guinea.

Although most of the Papua New Guinea highlands are too high for stable malaria transmission, local epidemics are a regular feature of the region. Few detailed descriptions of such epidemics are available, however. We describe the investigation of a malaria epidemic in the Obura Valley, Eastern Highlands Province, Papua New Guinea. Of the 244 samples examined by microscopy, 6.6% were positive for Plasmodium falciparum only, 9.4% were positive for Plasmodium vivax only, and 1.2% were mixed infections. MSP2 and MSP3alpha genotyping and AMA1 sequencing were used to determine the genetic variation present in a sample of P. falciparum and P. vivax infections. The P. vivax infections were found to be genetically highly diverse. In contrast, all P. falciparum samples were of a single genotype. This striking difference in genetic diversity suggests endemic, low-level local transmission for P. vivax but an outside introduction of P. falciparum as the most likely source of the epidemic.

Adolescent↗
PubMed2002

Cytokine responses during acute simian Plasmodium cynomolgi and Plasmodium knowlesi infections.

Experimental infection of non-human primates with simian malaria parasites offers a controlled system to study malarial immunity. Plasmodium cynomolgi (P. vivax-like) and P. knowlesi (P. falciparum-like) infections in the rhesus monkey were used as a model to test the hypothesis that initial acute infection stimulates type 1/pro-inflammatory cytokine expression followed by a gradual type 2/anti-inflammatory response upon re-infection. This study analyzed cytokine gene expression (interleukin-12, interferon-gamma, tumor necrosis factor-alpha = type 1; interleukin-4, interleukin-10 = type 2) using a semi-quantitative reverse transcriptase-polymerase chain reaction in monkeys infected with each of the parasites (three per group). Clinicoparasitologic and serologic parameters were also monitored. Monkeys were re-infected to assess whether enhanced immunity could increase parasite clearance. The immune response to P. cynomolgi infection in rhesus monkeys seemed to be mediated by anti-parasite, pro-inflammatory responses during primary infection with a transition to protective type 2 responses after repeat infection. The immune responses to P. knowlesi infection were more varied. Anti-inflammatory responses were more prevalent during primary infection. Repeat infection stimulated a wide variety of responses; most included expression of tumor necrosis factor-alpha, a cytokine that has been associated with inflammatory and host-destructive effects (weight loss, fever, anemia). These observations further confirmed that the simian malaria/rhesus monkey model is well suited for studies on the regulation of immunity to acute Plasmodium infection.

Acute Disease↗
PubMed2000

[Congenital malaria due to Plasmodium falciparum and Plasmodium malariae].

Increasing tourism and growing numbers of immigrants from malaria-endemic countries are leading to a higher importation rate of rare tropical disorders in European countries. We describe, to the best of our knowledge, the first case of connatal malaria in Austria. The patient is the first child of a 24 year old mother who was born in Ghana and immigrated to Austria one and a half years before delivery. She did not stay in an endemic region during this period and did not show fever or any other signs of malaria. The boy was healthy for the first six weeks of his life. In the 8th week of life he was admitted to our hospital due to persistent fever of unknown origin. On physical examination he showed only mild splenomegaly. Routine laboratory testing revealed mild hemolytic anemia with a hemoglobin value of 8.3 g/l. In the blood smear Plasmodium falciparum and Plasmodium malariae were detected. Oral therapy with quinine hydrochloride was successful and blood smears became negative for Plasmodia within 6 days. This case shows that congenital malaria can occur in children of clinically healthy women who were born in malaria-endemic areas even one and a half year after they have immigrated to non-endemic regions.

Adult↗
PubMed1979

Studies on the 2,4-diamino-6-substituted quinazolines. III. The capacity of sulfadiazine to enhance the activities of WR-158,122 and WR-159,412 against infections with various drug-susceptible and drug-resistant strains of Plasmodium falciparum and Plasmodium vivax in owl monkeys.

Previous studies showed: 1) that the activities of the 2,4-diamino-6-substituted quinazolines. WR-158,122 and WR-159,412, against Plasmodium falciparum and Plasmodium vivax infections in owl monkeys, were seriously impaired when infecting strains were pyrimethamine-resistant; and 2) that primary treatment failure with either agent led frequently to emergence of parasites resistant to these derivatives. Taking advantage of the potencies of WR-158,122 and WR-159,412 as dihydrofolic acid reductase inhibitors, the current studies were aimed at determining whether the above liabilities could be reduced to manageable levels or eliminated by concomitant administration of a rho-aminobenzoic acid inhibitor such as sulfadiazine. Application of these combinations prevented emergence of parasites resistant to WR-158,122 or WR-159,412, but did not abolish the differences in effectiveness of either compound against infections with pyrimethamine-susceptible and pyrimethamine-resistant strains; however, activities against infections with either susceptible or resistant strains were enhanced markedly. With WR-158,122, this enhancement ranged from greater than 7-fold to 75-fold; with WR-159,412, it ranged from greater than 5-fold to 13-fold. Maximal increases in activity were attained with a remarkedly small dose of sulfadiazine, 5.0 mg per kg of body weight daily. With this augmentation of activity, acceptably small doses of WR-158,122 regularly cured infections with even the most highly pyrimethamine-resistant strain.

Animals↗
PubMedDate not supplied

16alpha-bromoepiandrosterone, a dehydroepiandrosterone (DHEA) analogue, inhibits Plasmodium falciparum and Plasmodium berghei growth.

Dehydroepiandrosterone (DHEA) and its analogue, 16alpha-bromoepiandrosterone (alpha-epi-Br), may have activity against viral and parasitic infections, including human immunodeficiency virus (HIV) and Cryptosporidium parvum. Therefore, we evaluated its antimalarial effects on Plasmodium falciparum and Plasmodium berghei. In vitro, chloroquine (CQ)-sensitive and resistant strains of P. falciparum parasitized red blood cells were incubated with escalating doses of alpha-epi-Br or CQ. In vivo, 62 rats were infected with P. berghei and treated with CQ or alpha-epi-Br. At the highest doses tested against a CQ-sensitive strain, parasitemias decreased from 25.4% in the saline control group to 4.3% and 4.8% in the alpha-epi-Br and CQ groups, respectively (P < 0.05). Against two CQ-resistant strains, parasitemias decreased from 22.3-28.8% and 24.8-30% in the CQ and saline groups, respectively, to 2.5-2.7% in the alpha-epi-Br groups (P = 0.003). In vivo, on Day 4, parasitemias decreased from 23% in the saline group to 9-12% and 12% in the in alpha-epi-Br and CQ groups, respectively (P < 0.05). These data demonstrate that alpha-epi-Br shows activity against CQ-sensitive and resistant strains of P. falciparum in vitro. At the doses tested against P. berghei in vivo in rats, alpha-epi-Br is comparable to CQ.

Androsterone↗
PubMed1979

Factors affecting the in vitro culture of Plasmodium falciparum and Plasmodium knowlesi.

Plasmodium falciparum and Plasmodium knowlesi have been established in continuous culture using the basic method of Trager & Jensen. Various parameters of the culture system have been examined, namely, the gas requirements, serum and red cell requirements, frequency of medium replacement, and a comparison of static and agitated cultures made. The most important factors affecting growth in vitro seem to be the oxygen tension, red cell concentration, the frequency with which old medium is replaced, and the use of appropriate sera. Preliminary results indicate that horse serum may be possible as a replacement for human serum. Initial studies with P. knowlesi indicate that in the course of adapting to culture, parasites may change their antigenic specificity.

Animals↗
PubMed1999

[Evaluation of immunochromatographic test in the diagnosis of Plasmodium falciparum and Plasmodium vivax].

AIM: To evaluate the effectiveness of immunochromatographic test(ICT) in detecting Plasmodium falciparum and Plasmodium vivax in malaria endemic areas. METHODS: ICT was used to detect P. falciparum and P. vivax among patients with fever in the outpatient clinics by comparason with thick blood smear method. RESULTS: The sensitivity of ICT to detect P. falciparum and P. vivax was 96.7% and 90.4%, respectively. The specificity of ICT was 98.6%, and the coincidence rate was 94.7%. There is no cross reaction between P. falciparum and P. vivax. CONCLUSION: ICT could detect P. falciparum and P. vivax simutaneously, being more rapid and simple than blood smear method.

Animals↗
PubMed2000

[Practicability of IFAT using Plasmodium cynomolgi and Plasmodium falciparum antigens in different malarious areas].

OBJECTIVE: To compare the practicability of IFAT in different malarious areas using Plasmodium cynomolgi(P.c.) and Plasmodium falciparum(P.f.) antigens. METHODS: This survey was carried out in Yaliang Township of Sanya City, Hainan Province, where a mixed malaria is endemic, and in Tongbo County, Henan Province where only vivax malaria is endemic, and in Weihui City, Henan Province where vivax malaria has been under effective control since 1994-1998. RESULTS: In Yaliang Township, 310 blood samples were examined, the antibody positive rates with P.c. and P.f. were 37.4% and 31.3%, respectively, the rate of coincidence being 83.9%. In Tongbo County, 300 blood samples were examined. The antibody positive rates with P.c. and P.f. were 23.0% and 9.7%, respectively (P < 0.01). Another 245 blood samples from children were examined in Weihui City and the antibody positive rates were below 1% with two antigens, while the positive antibody rate was 3.3% with P.f. antigen. CONCLUSION: Both P.f. and P.c. antigens could be used in malaria antibody surveillance in mixted endemic areas, while in vivax malaria endemic areas, P.c. antigen was recommended.

Animals↗
PubMed2003

Rapid diagnostic devices for malaria: field evaluation of a new prototype immunochromatographic assay for the detection of Plasmodium falciparum and non-falciparum Plasmodium.

The NOW ICT Malaria P.f./P.v. for Whole Blood (Binax, Inc., Portland, ME) is a new malaria rapid diagnostic device that represents a technical advance over previous assays, such as ICT Malaria P.f./P.v. and ICT Malaria P.f.. We evaluated this device in March 2001 in symptomatic patients at malaria clinics in Maesod, Thailand. Microscopic examination of Giemsa-stained blood smears was the reference standard. In 246 patients, microscopy showed 32 (13.0%) infected with Plasmodium falciparum, 63 (25.6%) with P. vivax, 6 (2.4%) with mixed infections of P. falciparum and P. vivax, 5 (2.0%) with P. malariae, and 140 (56.9%) negative. Sensitivity for P. falciparum was 100% and specificity was 96.2% (200 of 208; 95% confidence interval [CI] = 92-98). For P. vivax, sensitivity was 87.3% (55 of 63; 95% CI = 77-93) and specificity was 97.7% (173 of 177; 95% CI = 95-99), but all the four false-positive results were microscopically positive for P. malariae; thus, specificity for non-falciparum Plasmodium was 100%. These results suggest improved performance over NOW ICT predecessors.

Adult↗
PubMed1992

Muramyl peptide adjuvants for Plasmodium falciparum and Plasmodium vivax circumsporozoite vaccines in rodent model systems.

Circumsporozoite proteins from the malaria parasites Plasmodium falciparum and Plasmodium vivax were expressed at high levels in the yeast Saccharomyces cerevisiae. Recombinant proteins varied both in length and in number of the natural amino acid repeat motifs. The proteins were purified and used to immunize mice, guinea pigs, and rabbits. Novel muramyl peptide adjuvants were used that increased the immune response as measured by ELISA assays, indirect immunofluorescence of fixed sporozoites, and the invasion of cultured liver cells by live sporozoites. These results suggest that an improved humoral response to recombinant circumsporozoite vaccines might be achieved by varying the design of the recombinant protein and by the use of novel adjuvant systems.

Adjuvants, Immunologic↗