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PubMed1999

In vivo responses to antimalarials by Plasmodium falciparum and Plasmodium vivax from isolated Gag Island off northwest Irian Jaya, Indonesia.

There is renewed interest in the rich nickel and cobalt deposits of Pulau Gag, an isolated but malarious island off the northwest coast of Irian Jaya. In preparation for an expanded workforce, an environmental assessment of malaria risk was made, focusing upon malaria prevalence in the small indigenous population, and the in vivo sensitivity of Plasmodium falciparum and P. vivax to chloroquine (CQ) and sulfadoxine/pyrimethamine (S/P), the respective first- and second-line drugs for uncomplicated malaria in Indonesia. During April-June 1997, mildly symptomatic or asymptomatic malaria infections were found in 24% of 456 native residents. Infections by P. falciparum accounted for 60% of the cases. Respective day 28 cure rates for CQ (10 mg base/kg on days 0 and 1; 5 mg/kg on day 2) in children and adults were 14% and 55% (P < 0.005). Type RII and RIII resistance characterized only 5% of the CQ failures. Re-treatment of 36 P. falciparum CQ treatment failures with S/P (25 mg/kg and 1.25 mg/kg, respectively) demonstrated rapid clearance and complete sensitivity during the 28-day follow-up period. More than 97% of the P. vivax malaria cases treated with CQ cleared parasitemia within 48 hr. Three cases of P. vivax malaria recurred between days 21 and 28, but against low drug levels in the blood. The low frequency of RII and RIII P. falciparum resistance to CQ, the complete sensitivity of this species to S/P, and the absence of CQ resistance by P. vivax are in contrast to in vivo and in vitro test results from sites on mainland Irian Jaya.

Adolescent↗
PubMed2002

Comparison of field and expert laboratory microscopy for active surveillance for asymptomatic Plasmodium falciparum and Plasmodium vivax in western Thailand.

Microscopy of Giemsa-stained thick and thin films by a skilled microscopist has remained the standard laboratory method for the diagnosis of malaria. However, diagnosis of malaria with this method is problematic since interpretation of results requires considerable expertise, particularly at low parasite levels. We compared the efficacy of "field" and "expert laboratory" microscopy for active surveillance of Plasmodium falciparum and P. vivax in western Thailand. Field microscopy consisted of an approximately five-minute read (50-100 fields) of a thick film at x700 using a natural light source, whereas expert laboratory microscopy consisted of a 20-minute read (number of parasites per 500 leukocytes) at x1,000 using a high-quality, well-maintained microscope with an artificial light source. All discordant and 20% of concordant results were cross-checked blindly. A total of 3,004 blood films collected between May and November 2000 were included in the study, of which 156 (5.2%) were positive for P. falciparum, 177 (5.9%) for P. vivax, and 4 (0.1%) for both P. falciparum and P. vivax by expert microscopy. A total of 84.4% (135 of 160) of the P. falciparum-positive slides and 93.9% of the P. vivax-positive slides had a parasitemia of less than 500/microL. Field microscopy was specific (99.3%) but not sensitive (10.0%) for the diagnosis of P. falciparum malaria, with a positive predictive value (PPV) of 43.2% and a negative predictive value (NPV) of 95.1%. The corresponding specificity and sensitivity for the diagnosis of P. vivax malaria were 99.2% and 7.1%, respectively, with a PPV of 38.7% and an NPV of 93.9%. Field microscopy, as defined in this study, is not an effective method for active malaria surveillance in western Thailand, where prevalence and parasitemia rates are low.

Adolescent↗
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

Evolution of Plasmodium and the recent origin of the world populations of Plasmodium falciparum.

We have investigated the evolution of Plasmodium parasites by analyzing DNA sequences of several genes. We reach the following conclusions: (1) The four human parasites, P. falciparum, P. malariae, P. ovale, and P. vivax are very remotely related to each other, so that their evolutionary divergence predates the origin of the hominids; several of these parasites became associated with the human lineage by lateral transfer from other hosts. (2) P. falciparum diverged from P. reichenowi about 8 million years ago, consistently with the time of divergence of the human lineage from the apes; a parsimonious inference is that falciparum has been associated with humans since the origin of the hominids. (3) P. malariae is genetically indistinguishable from P. brasilianum, a parasite of New World monkeys; and, similarly. (4) P. vivax is genetically indistinguishable from the New World monkey parasite P. simium. We infer in each of these two cases a very recent lateral transfer between the human and monkey hosts, and explore alternative hypotheses about the direction of the transfer. We have also investigated the population structure of P. falciparum by analyzing 10 genes and conclude that the extant world populations of this parasite have evolved from a single strain within the last several thousand years. The extensive polymorphisms observed in the highly repetitive central region of the Csp gene, as well as the apparently very divergent two classes of alleles at the Msa-1 gene, are consistent with this conclusion.

Amino Acid Sequence↗
PubMed1997

Evaluation of the sensitivity in vitro of Plasmodium falciparum and in vivo of Plasmodium chabaudi Malaria to various drugs and their combinations.

K1 strain of Plasmdoium falciparum is resistant in vitro to chloroquine, pyrimethamine and sulfadoxine. Response of this strain to combinations of antimalarial drugs in the in vitro hypoxanthine incorporation test was coupled with that of a line of strain NF54 relatively sensitive to chloroquine and fully sensitive to other antimalarials. Pyrimethamine and sulfadoxine showed potentiative synergism against NF54 and less marked against K1. Erythromycin and chloroquine showed potentiation, but less marked against NF54. Quinine and clindamycin had an additive effect against NF54 but potentiated against K1. Combinations of chloroquine with quinine or amodiaquine or of amodiaquine with clindamycin or erythromycin showed mild antagonistic or additive effects. In vivo studies in mice, using the 4-day suppressive test, the AS(3CQ) clone of Plasmodium chabaudi was resistant to pyrimethamine and chloroquine but sensitive to sulfadoxine. Similar combinations as above were carried out and their responses were compared between the resistant and sensitive strains. For both strains, the combinations of chloroquine-erythromycin, pyrimethamine-sulfadoxine, quinine-clindamycin showed potentiation; antagonistic effects were observed in chloroquine-amodiaquine combinations whereas when amodiaquine combined with erythromycin the effect was additive. Amodiaquine-clindamycin and chloroquine-quinine combinations have an antagonistic effect against the sensitive strain but additive against the resistant strain.

Animals↗
PubMed1979

Studies on the 2,4-diamino-6-substituted quinazolines. II. Activities of selected derivatives against infections with various drug-susceptible and drug-resistant strains of Plasmodium falciparum and Plasmodium vivax in owl monkeys.

Four 6-thio-, one 6-sulfinyl-, and two 6-sulfonyl-substituted 2,4-diaminoquinazolines were evaluated for capacities to cure established infections with the chloroquine-resistant Vietnam Oak Knoll and pyrimethamine-resistant Malayan Camp-CH/Q strains of Plasmodium falciparum in owl monkeys. As compared with the doses of standard drugs required for cure of infections with drug-susceptible strains or doses of the newly developed aminoalcohols required for cure of either drug-susceptible or drug-resistant strains, each of these quinazolines effected cure of infections with the Oak Knoll strain at a remarkably small daily dose. However, doses required for cure of infections with the Camp-CH/O strain were from 4-48 times those required for cure of infections with the Oak Knoll strain, suggesting that the activities of these quizanolines, like those of 6-amino-substituted derivatives, were compromised by pyrimethamine resistance. This suggestion received support from expanded studies involving WR-158,122 and WR-159,412, the most active of the agents examined, and the multidrug-resistant Vietnam Smith strain of P. falciparum and Vietnam Palo Alto strain of P. vivax, as well as the Oak Knoll and Camp-CH/Q strains. These studies also showed that significant fractions of infections with the Oak Knoll, Camp-CH/Q, and Palo Alto strains treated previously with subcurative doses of the above derivatives failed to respond to doses that regularly cured previously untreated infections. These treatment failures proved to be due to emergence of parasites resistant to the quinazolines.

Animals↗
PubMed1999

[Studies on detection of Plasmodium falciparum and Plasmodium vivax in blood samples by multiplex polymerase chain reaction].

AIM: To establish a sensitive and specific PCR-based method to detect Plasmodium falciparum and P. vivax in blood samples in a single amplification reaction. METHODS: Malaria parasite DNA in blood was amplified by the multiplex polymerase chain reaction using two sets of primers derived from the P. f. moderately-repetitive DNA sequence and COIII gene of P.v. RESULTS: A 206-bp product for P. f. and a 370-bp product for P.v. were amplified by multiplex PCR, being able to detect parasitemia level as low as 5 x 10(-7) for P. f. and 1.02 x 10(-6) for P. v. and having no cross-reaction with human leucocyte DNA. A total of 783 blood samples on the filter paper collected from patients attending to malaria clinics in malaria endemic areas were detected. The positive rate of multiplex PCR was 85.8%, the misdiagnosis rate was 0, and the under-diagnosis rate was 0.1%, while these three rates of microscopic examination were 84.9%, 3.1% and 1.0%, respectively. The concordance between the two methods was 95.8%. CONCLUSION: The multiplex PCR method made the malaria detection more sensitive and specific than the microscopic examination and should be suitable for the diagnosis of malaria in mixed endemic areas, large-scale epidemiological studies, follow-up of drug treatment and donor blood screening.

Animals↗
PubMed1964

POTENTIATION OF ACTIVITY OF DIAPHENYLSULFONE AND PYRIMETHAMINE AGAINST PLASMODIUM GALLINACEUM AND PLASMODIUM CYNOMOLGI BASTIANELLII.

In view of the fact that diaphenylsulfone has been shown to have low schizontocidal activity against Plasmodium gallinaceum and to lead to resistance in strains of P. cynomolgi, investigations were undertaken into the joint action of diaphenylsulfone and pyrimethamine against P. gallinaceum in chicks and P. cynomolgi bastianellii in monkeys. These drugs were assayed separately and in various combinations. It was found that at certain dose levels combination of the two drugs led to potentiation of their plasmocidal activity. On the other hand, this synergistic effect was not noted with combinations containing lower dosages of either drug; with these, a simple additive effect occurred. The authors suggest that the two drugs probably act on the same metabolic pathway but that their points of attack may be different. They note also that there was a difference in the response of P. gallinaceum in chicks and of P. cynomolgi bastianellii in monkeys to the combined use of the two drugs.

Animals↗
PubMed1991

Antimalarial activity of crude extracts from Brazilian plants studied in vivo in Plasmodium berghei-infected mice and in vitro against Plasmodium falciparum in culture.

1. Ninety-five crude extracts obtained with either organic solvents or water from 48 Brazilian plants or parts of plants were evaluated experimentally as blood schizontocides. Seventy-three extracts were obtained from 33 plants randomly collected using an empirical approach, and 22 from 15 "medicinal" plants. 2. The crude extracts were screened in vivo at up to 1.0 g/kg, po, for 4 days in mice infected with blood forms of Plasmodium berghei and parasitemia was determined on the fifth day. 3. Six plants, 2 randomly collected, Vernonia brasiliana and Eupatorium squalidum, and 4 "medicinal" plants, Acanthospermum australe, Esenbeckia febrifuga, Lisianthus speciosus, and Tachia guianensis, were partly active against the rodent malaria, i.e., they showed 40-50% inhibition of P. berghei multiplication. Forty-two plants whose extracts presented no antimalarial activity are reported. 4. Four extracts with antimalarial activity were also tested in vitro using P. falciparum cultures and two of them, V. brasiliana and A. australe, were active. Extracts of V. brasiliana caused about 50% inhibition of parasite multiplication at relatively low doses (40 ng/ml) as compared to chloroquine (30 ng/ml) and quinine (50 ng/ml). 5. The relatively high percentage of positive results obtained here for "medicinal" plants vs randomly chosen plants demonstrates the effectiveness of the ethnopharmacological approach to drug testing.

Animals↗
PubMed1991

Tissue schizontocidal effect of trifluoroacetyl primaquine in Plasmodium yoelii infected mice and Plasmodium cynomolgi infected monkeys.

Trifluoroacetyl primaquine oxalate (M8506) was compared with primaquine phosphate for tissue schizontocidal action in rodent and simian malaria. In Plasmodium yoelii sporozoites infected mice, the causal prophylactic effects of M8506 at 5, 10 and 20 mg(base)/kg were 56.7%, 87.2% and 100%, respectively, comparable to those of primaquine (54.4%, 90.8% and 100%). In P. cynomolgi sporozoites infected rhesus monkeys 4 dosage regimens of the two agents were compared for radical curative effect. On the first day of treatment pyronaridine phosphate 10 mg(base)/kg twice a day were intramuscularly injected to eliminate erythrocytic stages of P. cynomolgi. At the dosage of 3.0 mg(base)/kg/day x 3, both M8506 and primaquine radically cured the monkeys. At 0.75 mg/kg/day x 3, 12 of 13 (92.3%) monkeys cured by M8506, 5 of 9 (55.6%) cured by primaquine. At 1.5 and 0.375 mg/kg/day x 3, the radical curative effects of M8506 were also better than those of primaquine. Since the toxicity of M8506 was significantly milder in mice, rats and dogs than that of primaquine, M8506 has potential as a tissue schizontocide.

Aminoquinolines↗
PubMed1988

Characterization of cross-reactive blood-stage antigens of the Plasmodium cynomolgi complex using anti-Plasmodium vivax monoclonal antibodies.

Five out of 18 monoclonal antibodies (moAB's) produced against blood stages of a Brazilian (Belem) strain of Plasmodium vivax were shown to cross-react with all of the 11 strains of the P. cynomolgi complex that were assayed. The 5 moAB's produced 3 different patterns of immunofluorescence, identical for both P. vivax and P. cynomolgi. Three of these moAB's appeared to react with antigens associated with the cytoplasm or membranes of infected erythrocytes. By Western blot analysis, 2 of these 3 moAB's identified an antigen with an apparent molecular weight of 31 kDa in extracts of parasitized erythrocytes of both species; the third of these moAB's reacted with an antigen with an apparent molecular weight of 95 kDa. By immunofluorescence, the 2 other moAB's reacted only with parasites at all developmental stages. The target antigen of these 2 moAB's was not identified. Immunoradiometric assays indicated that the moAB's are directed against 3 or possibly 4 distinct nonrepetitive epitopes. None of the moAB's inhibited merozoite invasion or growth of the parasites in an in vitro culture system of the Berok strain of P. cynomolgi.

Animals↗
PubMed1989

Analysis of the sporogonic development of Plasmodium falciparum and Plasmodium berghei in anopheline mosquitoes.

Basic knowledge of the sporogonic development of malarial parasites is crucial when evaluating the sporontocidal activity of antimalarial drugs or when determining why certain vectors are refractory to a particular parasite while others are competent vectors. We have developed a model which we have used to i) assess the sporogonic development of Plasmodium berghei ANKA in Anopheles stephensi and A. freeborni mosquitoes and ii) determine the effect of chloroquine on the sporogony of P. falciparum NF-54 in A. stephensi. Criteria used to assay sporogonic development include: i) number of oocysts present, ii) percentage of mosquitoes with oocysts, iii) time of release of sporozoites from the oocysts into the hemolymph, iv) time and degree of sporozoite invasion of salivary glands, and v) transmission (P. berghei) into vertebrate hosts. Parasite development in the mosquito is evaluated every other day, commencing on ca. day 7 post-feed (PF) and continuing until ca. day 22 PF. These detailed observations allow us to delineate the chronology of sporogonic development.

Animals↗
PubMed1986

Immunoregulatory alterations in Plasmodium falciparum and Plasmodium vivax infections.

Studies on the immune function of patients with acute Plasmodium vivax or P. falciparum infections were performed. All subjects were residing in recent malaria endemic areas of Venezuela. Lymphopenia, reduction of peripheral blood T-lymphocytes positive for monoclonal antibody OKT4 (T helper) a decrease of in vitro mitogenic proliferative response and natural killer cell activity were observed. Serum lymphocytotoxic antibodies reactive at 37 degrees C were detected in both groups of patients as well as serum autoantibodies. The possible role of lymphocytotoxic autoantibodies in the etiology of the T-lymphocyte depletion and acquired immunological perturbations in human malaria is discussed.

Antilymphocyte Serum↗
PubMed1988

[Efficacy of halofantrine in Plasmodium falciparum or Plasmodium vivax malaria in a resistance area (French Guiana)].

Halofantrine (WR 171.669) is a phenanthrene methanol derivative effective against the multidrug resistant strains of Plasmodium falciparum. One hundred and one patients, 48 men and 53 women, 53 adults and 48 children (less than or equal to 12 years old) aged from 1.5 to 57 years were treated. Fifty-one patients received a single 16 mg/kg dose and 50 patients received 24 mg/kg/day in 3 doses at 6-hour intervals. Parasite counts with examination of both thin and thick smears were performed twice daily for 5 to 6 days following treatment, or until smears were negative for parasites for 24 hours, and then weekly for 4 weeks. Thirteen patients reported clinical side effects. Six treated patients had no parasites. One patient had mixed parasitemia. Eighty three patients had P. falciparum malaria, with mean parasitemias between 26,850 +/- 36,679 and 35,412 +/- 50,527 per cubic millimeter. Halofantrine was very effective in the two doses tested from 87.5 to 100 p. 100. Eleven patients had in vivo resistant strains; ten in vitro tests were successful and nine were resistant to chloroquine. Thirteen patients with P. vivax and a mean parasitemia of 13,858 +/- 10,835 per cubic millimeter were cured but 3 had a relapse 3 to 4 weeks after treatment. At the 2 dosage levels tested halofantrine proved highly effective in the treatment of malaria caused by resistant and sensitive strains to P. falciparum.

Adolescent↗
PubMed1980

Plasmodium falciparum and Plasmodium vivax infections in Saudi Arabia, with a note on the distribution of anopheline vectors.

Variations in the intensity of Plasmodium infections were observed in the surveyed regions of Saudi Arabia. The highest incidence had been recorded from the Southern region and the lowest form the Northern and Eastern regions. The Western region, however, showed a regular and uniform occurrence of infection throughout the year. Five anopheline vectors were identified in the country.

Animals↗
PubMed1980

Chemosuppressive field trials in Thailand. IV. The suppression of Plasmodium falciparum and Plasmodium vivax parasitemias by mefloquine (WR 142,490, A 4-quinolinemethanol).

The effect of various dosages of mefloquine hydrochloride (WR 142,490) and sulfadoxine-pyrimethamine in the suppression of malaria infections was studied in an area of northeastern Thailand highly endemic for both chloroquine-resistant Plasmodium falciparum and for P. vivax. Both preparations, in all regimens studied, were effective in greatly reducing the incidence of falciparum infections. Mefloquine was more active in preventing vivax parasitemia than sulfadoxine-pyrimethamine; however, this combination remains the commercially available regimen of choice where both parasites occur and P. falciparum is resistant to chloroquine.

Adolescent↗
PubMed1993

Experimental infection of Anopheles gambiae s.s., Anopheles freeborni and Anopheles stephensi with Plasmodium malariae and Plasmodium brasilianum.

Susceptibility to infection of 2 strains of Anopheles gambiae s.s., An. freeborni and An. stephensi, was determined for 2 closely related malaria parasites, Plasmodium malariae and P. brasilianum. Neither strain of An. gambiae supported development of oocyst densities as great as the other 2 anopheline mosquitoes. The ZAN strain of An. gambiae s.s. from Zanzibar was more susceptible to infection with the strain of P. malariae from Uganda than the G-3 strain of An. gambiae s.s. from The Gambia. All species and strains of mosquitoes supported complete development to the presence of sporozoites in the salivary glands.

Animals↗
PubMed2002

Plasmodium falciparum: glycosylation status of Plasmodium falciparum circumsporozoite protein expressed in the baculovirus system.

We expressed the main surface antigen of Plasmodium falciparum sporozoites, the circumsporozoite protein (CSP), in High Five (Trichoplusia ni) insect cells using the baculovirus system. Significant amounts of the recombinant protein could be obtained, as judged by SDS-PAGE, Western blot, and immunofluorescence analysis. The cellular localization for recombinant CSP was determined by immunofluorescence. The high fluorescence signal of the permeabilized cells, relative to that of fixed nonpermeabilized cells, revealed a clear intracellular localization of this surface antigen. Analysis of possible posttranslational modifications of CSP showed that this recombinant protein is only N-glycosylated in the baculovirus system. Although DNA-sequence analysis revealed a GPI-cleavage/attachment site, no GPI anchor could be demonstrated. These analyses show that the glycosylation status of this recombinant protein may not reflect its native form in P. falciparum. The impact of these findings on vaccine development will be discussed.

Animals↗