PubMed Health⌕ Search

Biomedical subjects

P I Trigg

Publications and source records attributed to P I Trigg.

At least 19 recordsLinked to original sources
PubMed1999

Malaria control priorities and constraints.

Each year, there are still between 300-500 million clinical cases of malaria and over one million deaths due to the disease, 90% of which occur in Africa south of the Sahara. In all continents, malaria risk is highest in remote rural areas where poverty abounds, population densities are low and the quality and coverage of the health services are poor or in existent. A sustained impact on the malaria burden can only be achieved through the cost-effective use of current tools, by including malaria in health sector development and inter-sectorial action, by mobilizing malaria control within communities and by investing in new and more effective tools. This paper highlights some of the constraints faced by countries in controlling malaria and outlines the priority activities that are being carried out to address these constraints within both communities and the health services. It aims to be set the scene for the papers of this Centenary book which address some of these issues in more detail.

Bedding and Linens↗
PubMed1998

Commentary: malaria control in the 1990s.

In May 1955 the Eighth World Health Assembly adopted a Global Malaria Eradication Campaign based on the widespread use of DDT against mosquitos and of antimalarial drugs to treat malaria and to eliminate the parasite in humans. As a result of the Campaign, malaria was eradicated by 1967 from all developed countries where the disease was endemic and large areas of tropical Asia and Latin America were freed from the risk of infection. The Malaria Eradication Campaign was only launched in three countries of tropical Africa since it was not considered feasible in the others. Despite these achievements, improvements in the malaria situation could not be maintained indefinitely by time-limited, highly prescriptive and centralized programmes. Also, vector resistance to DDT and of malaria parasites to chloroquine, a safe and affordable drug, began to affect programme activities. A global Malaria Control Strategy was endorsed by a Ministerial Conference on Malaria Control in 1992 and confirmed by the World Health Assembly in 1993. This strategy differs considerably from the approach used in the eradication era. It is rooted in the primary health care approach and calls for flexible, decentralized programmes, based on disease rather than parasite control, using the rational and selective use of tools to combat malaria. The implementation of the Global Strategy is beginning to have an impact in several countries, such as Brazil, China, Solomon Islands, Philippines, Vanuatu, Viet Nam and Thailand. The lesson from these areas is clear: malaria is being controlled using the tools that are currently available. The challenge is now to apply these tools among vulnerable individuals and groups experiencing high levels of morbidity and mortality, particularly in sub-Saharan Africa, for which long-term investments are required.

DDT↗
PubMed1997

Global overview of malaria.

Malaria continues to be one of the main public health problems in the world, especially in the majority of African countries. It particularly affects young children, young adults engaged in economic development activities, pregnant women and international itinerant groups of population, moving into malaria endemic areas. Malaria epidemics became a regular feature in many parts of the world, including the highlands of Africa, being associated with the warming of the climate, disruption of health services and large scale uncontrolled population movement as a result of social disruption and civil wars. Further proliferation of drug resistance is closely related to massive population movements, inadequate health services, improper use of antimalarial drugs, limited resources and operational difficulties in implementing malaria control activities. The economic impact of malaria is felt by various social groups of the society particularly by the poorest countries of the world and among populations living under the most difficult conditions. To overcome the malaria challenge, there is a need for concerted efforts by the health services, the private sector, the communities themselves, including the international community. Much could be achieved through the research and development (the use of insecticide-impregnated materials) and disease management (the use of artemisinin and its derivatives in areas with multi-drug resistance) will facilitate the achievement of the global goal of malaria control-to eliminate mortality and to reduce morbidity due to malaria.

Adult↗
PubMed1995

Status of antimalarial drugs under development.

Despite the urgent need of a new antimalarial drugs, particularly those against multiresistant falciparum malaria, only a limited number of drugs are now at an advanced stage of preclinical or clinical development. They include artemisinin derivatives, pyronaridine and benflumetol (all originally developed in China), as well as new antifolate combinations, the hydroxynaphoquinone atovaquone which has a novel mode of action, and a new 8-aminoquinoline which appears more active and less toxic than primaquine. Some of these drugs may become available in the next few years. It is therefore essential to find mechanisms to ensure that they are made available at an affordable price to the populations that really need them.

Antimalarials↗
PubMed1987

A phase II/III double-blind, dose-finding clinical trial of a combination of mefloquine, sulfadoxine, and pyrimethamine (Fansimef) in falciparum malaria.

Fansimef is a combination of 250 mg mefloquine (base), 500 mg sulfadoxine, and 25 mg pyrimethamine per tablet. One hundred and fifty adult male Brazilian patients at Belém (Pará), who had peripheral blood smears positive for Plasmodium falciparum, with or without clinical symptoms of falciparum malaria, were treated in a double-blind randomized fashion with either one, two or three tablets of Fansimef. Of those receiving one tablet (48 patients), 81% were cured and 19% exhibited RI recrudescences. All the patients receiving two or three tablets of Fansimef (49 patients in each group) were cured. The rates of initial clearance of parasitaemia and fever were similar in all treatment groups. Tolerance was good at all dose levels. The main side-effects included nausea, vomiting, dizziness, diarrhoea and abdominal pain, but these were mild and transient and required no specific treatment. The incidence of vomiting and nausea was highest in patients given the three-tablet dose. The results of various haematological, biochemical and urine analyses were not adversely altered by the administration of Fansimef.

Administration, Oral↗
PubMed1985

Recent advances in malaria parasite cultivation and their application to studies on host-parasite relationships: a review.

The continuous cultivation of the erythrocytic stages of Plasmodium falciparum was achieved in 1976 and techniques have now also been developed for continuous cultivation of these stages from P. knowlesi, P. fragile, P. inui, P. cynomolgi and P. berghei. The requisite conditions for successful cultivation are described. Gametes of certain isolates of P. falciparum can also now be produced in vitro and these are infective to mosquitos, leading to normal development of the parasite.The successful cultivation in vitro of the exoerythrocytic stages of P. berghei and P. vivax was achieved in 1981 and 1983, respectively. These cultures give rise to infective merozoites.There have been no significant advances in the in vitro cultivation of the sporogonic stages of malaria parasites for the last 15 years, although studies indicate that the in vitro cultivation of these stages from gamete to sporozoite stage is theoretically possible.The application of cultivation techniques to the study of parasite epidemiology is discussed. To date the major epidemiological impact has related to their use for measuring the incidence and spread of drug resistance. Applications to the study of the genetics of drug resistance, antigen production, development of tests for protective immunity, and drug development and screening are reviewed.

Animals↗
PubMed1981

Double diffusion analysis of antigens released from Plasmodium knowlesi in vitro.

Two parasite-derived antigens (designated band 1 and band 2) were identified upon double-diffusion analysis of culture medium from reinvading culture of P. knowlesi. Band 1 antigen showed characteristics with the R-antigens of P. falciparum while the other was similar to the P. falciparum L-antigens. Both antigens appeared to be largely particulate in character and did not display any obvious variant-specificity. Analysis of plasma from rhesus monkeys infected with the same antigenic variant showed the presence of band 1 antigen only.

Animals↗
PubMed1980

Inhibition of malaria parasite invasion into erythrocytes pretreated with membrane-active drugs.

Normal rhesus monkey erythrocytes were incubated with various membrane-active drugs (for 1 h at 37 degrees C) and after thorough washing, were exposed to infection with Plasmodium knowlesi in an invitro cultivation system. The ability of merozoites to infect with drug-pretreated erythrocytes was assessed both by counting the number of infected cells and by measuring the incorporation of [3H]isoleucine into parasite protein. Marked inhibition of invasion was observed with vinblastine and colchicine, at concentrations greater than 5 x 10(-4) M, respectively. At similar concentrations, cytochalasin B or amantadine had no apparent effect. The addition of 10(-3) M 3',5'-cAMP to the medium during the incubation in the presence of colchicine or vinblastine partially decreased the inhibitory effects. The effects of colchicine and vinblastine on parasite invasion may be correlated with a reversible alteration in erythrocyte conformation (spherocytosis) which occurs at similar drug concentrations to those above and which can be relieved by simultaneous incubation with cAMP. A possible mechanism of action is proposed.

Alkaloids↗
PubMed1980

Analysis of proteins synthesized in vitro by the erythrocytic stages of Plasmodium knowlesi.

Studies were performed to identify specific parasite proteins synthesized within Plasmodium knowlesi-infected rhesus erythrocytes. Sodium didecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of whole parasites freed from the host erythrocyte by immune lysis, of membranous and cytoplasmic parasite fractions, and of isolated merozoites, detected several parasite-specific components after Coomassie Blue staining of the separated proteins. However, significant contamination with host erythrocyte material generally occurred, particularly in the whole parasite and parasite membrane preparations. Improved identification of plasmodial proteins was subsequently afforded by a radioisotope labelling technique in which parasitized erythrocytes were cultivated in vitro with [3H]isoleucine prior to electrophoretic analysis. Of 11 principal labelled peaks ranging in molecular weight from approximately 17000 to 145000 which were detected upon electrophoresis of whole parasites harvested from culture, all were observed in the cytoplasmic fraction while at least 5 were also associated with the membranous cell fraction. Analysis of different developmental stages of the intra-erythrocytic parasite revealed no significant stage-specific qualitative variations in the electrophoretic profiles. Quantitatively, however the middle to late trophozoites incorporated more [3H]isoleucine into protein than the other intra-erythrocytic stages. Analysis of merozoites purified from labelled schizonts showed a protein pattern similar to the other stages. This confirmed that host components did not contribute to the labelling pattern and that none of the labelled proteins were specific to the residual cytoplasm remaining after merozoite formation.

Animals↗
PubMed1980

Release of radio-isotope labelled antigens from Plasmodium knowlesi during merozoite re-invasion in vitro.

Labelled antigens sharing determinants with both membrane and cytoplasmic fractions of Plasmodium knowlesi were detected in culture medium after in vitro incubation of schizont-stage parasites previously pulse-labelled with [3H]isoleucine. Release of antigens occurred only during schizont rupture and merozoite re-invasion. Antigenic material accounted for up to a third of the total trichloroacetic acid-insoluble radioactivity released by the cells. Absorption experiments indicated that approximately two-thirds of this antibody-precipitable material shared determinants with parasite membrane antigens, with a similar quantity sharing determinants with cytoplasmic proteins. Using antisera derived against 2 different antigenic variants of P. knowlesi, no evidence for the release of variant-spcific antigens was obtained. Centrifugal analysis revealed that the majority of the radio-isotope labelled antigens were particulate in nature; however, some appeared to exist in true solution.

Animals↗
PubMed1979

Freeze fracture studies on the interaction between the malaria parasite and the host erythrocyte in Plasmodium knowlesi infections.

The freeze fracture technique has been used to study the internal cyto-architecture of the surface membranes of the parasite and erythrocyte in Plasmodium knowlesi infections. Six fracture faces, derived from the plasma membrane and 2 pellicular membranes, have been identified at the surface of the free merozoite. The apposed leaflets of the 2 pellicular membranes show the characteristic features of E fracture faces, a result compatible with the view that the pellicular membranes line a potential cisterna. There is evidence to suggest that there may be changes in the distribution and density of the integral proteins in the merozoite plasma membrane at invasion. Furthermore, vesicles consisting of stacked membranes occur within and around the erythrocyte invagination at invasion; it is suggested that these vesicles are released from the merozoite rhoptries. Formation of the parasitophorous vacuole is accompanied by dramatic changes in the density and distribution of intra-membraneous particles (IMP) in the vacuolar membrane. Initially there is a great reduction in particle numbers, but subsequently the particles reappear and show reversed polarity. The possible causes and implications of these changes are discussed. The intra-erythrocytic parasite synthesizes new transmembrane proteins as development proceeds, and the trophozoite and schizont stages of development are characterized by the appearance of circular, particle-free regions in the parasite plasmalemma. There is a decrease in the density of transmembrane proteins in the erythrocyte plasma membrane during parasite maturation, and the P face IMP show the characteristic features of aggregation.

Animals↗