Can anything be done to maintain the effectiveness of pyrethroid-impregnated bednets against malaria vectors?
Pyrethroid-treated bednets are the most promising available method of controlling malaria in the tropical world. Every effort should be made to find methods of responding to, or preventing, the emergence of pyrethroid resistance in the Anopheles vectors. Some cases of such resistance are known, notably in An. gambiae in West Africa where the kdr type of resistance has been selected, probably because of the use of pyrethroids on cotton. Because pyrethroids are irritant to mosquitoes, laboratory studies on the impact of, and selection for, resistance need to be conducted with free-flying mosquitoes in conditions that are as realistic as possible. Such studies are beginning to suggest that, although there is cross-resistance to all pyrethroids, some treatments are less likely to select for resistance than others are. Organophosphate, carbamate and phenyl pyrazole insecticides have been tested as alternative treatments for nets or curtains. Attempts have been made to mix an insect growth regulator and a pyrethroid on netting to sterilize pyrethroid-resistant mosquitoes that are not killed after contact with the netting. There seems to be no easy solution to the problem of pyrethroid resistance management, but further research is urgently needed. (+info)
gammadelta T cells contribute to control of chronic parasitemia in Plasmodium chabaudi infections in mice.
During a primary infection of mice with Plasmodium chabaudi, gammadelta T cells are stimulated and their expansion coincides with recovery from the acute phase of infection in normal mice or with chronic infections in B cell-deficient mice (mu-MT). To determine whether the large gammadelta T cell pool observed in female B cell-deficient mice is responsible for controlling the chronic infection, studies were done using double-knockout mice deficient in both B and gammadelta cells (mu-MT x delta-/-TCR) and in gammadelta T cell-depleted mu-MT mice. In both types of gammadelta T cell-deficient mice, the early parasitemia following the peak of infection was exacerbated, and the chronic parasitemia was maintained at significantly higher levels in the absence of gammadelta T cells. The majority of gammadelta T cells in C57BL/6 and mu-MT mice responding to infection belonged predominantly to a single family of gammadelta T cells with TCR composed of Vgamma2Vdelta4 chains and which produced IFN-gamma rather than IL-4. (+info)
Immunization of mice with DNA-based Pfs25 elicits potent malaria transmission-blocking antibodies.
Immunological intervention, in addition to vector control and malaria chemotherapy, will be needed to stop the resurgence of malaria, a disease with a devastating impact on the health of 300 to 500 million people annually. We have pursued a vaccination strategy, based on DNA immunization in mice with genes encoding two antigens present on the sexual stages of Plasmodium falciparum, Pfs25 and Pfg27, to induce biologically important antibodies that can block development of the parasite in the Anopheles mosquito and thus transmission of the disease. DNA encoding Pfs25 when administered by the intramuscular route, either alone or with DNA encoding Pfg27, had the most potent transmission-blocking effects, resulting in up to a 97% decrease in oocyst numbers in mosquito midguts and a 75% decrease in rate of infection. Immunization with DNA encoding a Pfg27-Pfs25 fusion protein was less effective and DNA encoding Pfg27 elicited antibodies in sera that had only modest effects on the infectivity of the parasite. These results show for the first time that DNA vaccination can result in potent transmission-blocking antibodies in mice and suggest that the Pfs25 gene should be included as part of a multicomponent DNA vaccine. (+info)
Antimalarial activities of various 9-phenanthrenemethanols with special attention to WR-122,455 and WR-171,669.
Pilot appraisals of the activities of 16 specially selected 9-phenanthrenemethanols against acute infections with Plasmodium falciparum in owl monkeys showed that all were more active than the reference compound, WR-33,063. WR-122,455, the most active derivative, and WR-171,669, ranked sixth, were selected for study in human volunteers. To assist this undertaking, appraisals of both compounds in owl monkeys infected with various strains of P. falciparum were expanded. These assessments showed: (i) that WR-122,455 was four times as active as chloroquine against infections with chloroquine-sensitive strains and that WR-171,669 equalled chloroquine in activity; (ii) that these compounds were fully active against infections with strains resistant to chloroquine, pyrimethamine, or quinine, or to all three standard drugs; (iii) that the activity of WR-122,455 was a function of total dose, single doses being as effective as the same amounts delivered in three or seven daily fractions; and (iv) that a single dose of WR-122,455 conferred extended, although only partial, protection against challenges with trophozoites. Complementary experiments in rhesus monkeys inoculated with sporozoites of P. cynomolgi showed that the activity of WR-122,455 was limited to blood schizonts and did not extend to early or late tissue schizonts. These evaluations were compatible with the results of preliminary studies of the activities of WR-122,455 and WR-171,669 in human volunteers. (+info)
Antimalarial activities of various 4-pyridinemethanols with special attention to WR-172,435 and WR-180,409.
Pilot appraisals of the activities of 10 specially selected 2,6-substituted-4-pyridinemethanols against acute Plasmodium falciparum infections in owl monkeys identified three derivatives that were two to three times as active as chloroquine against infections with a 4-aminoquinoline-susceptible strain and, at the same doses, were equally effective against infections with a strain fully resistant to treatment with maximally tolerated doses of chloroquine, quinine, and pyrimethamine. Two of these derivatives, WR-172,435 and WR-180,409, deemed worthy of evaluation in human volunteers, were studied in greater depth in owl monkeys infected with either the multidrug-resistant Smith strain of P. falciparum or the pyrimethamine-resistant Palo Alto strain of P. vivax. These studies showed (i) that at the same total oral dose, 3-day and 7-day treatment schedules were equally effective and slightly superior to a single-dose schedule; (ii) that WR-172,435 was slightly more active than WR-180,409 in each treatment regimen; (iii) that intravenous delivery of WR-180,409 phosphate was feasible and effective; (iv) that both compounds effected control of parasitemia more rapidly than any standard or newly discovered antimalarial drug; and (v) that WR-172,435 and WR-180,409 had therapeutic indexes at least four to eight times those exhibited by chloroquine in infections with 4-aminoquinoline-susceptible strains, indexes retained by these pyridinemethanols against infections with various drug-resistant strains. (+info)
Suppression of lymphocyte transformation by plasma from owl monkeys acutely infected with Plasmodium falciparum.
Plasma collected from owl monkeys during the acute phase of Plasmodium falciparum infection was shown to adversely affect several in vitro responses which are considered to be correlates of cell-mediated immune functions of normal monkeys. In the presence of acute-phase plasma, response of normal monkey peripheral blood lymphocytes to stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitogen was severely reduced, as was the ability of peripheral blood lymphocytes to respond to allogenic and xenogenic histocompatible antigens. The transformation response of peripheral blood lymphocytes from normal humans to phytohemagglutinin and concanavalin A was also suppressed. Since acute-phase plasma was not cytotoxic for peripheral blood lymphocytes, decreased responsiveness did not result from cell destruction. Acute-phase plasma appears to block initial steps in lymphocyte transformation. (+info)
Evaluating the community education programme of an insecticide-treated bed net trial on the Kenyan coast.
Increased interest in the potential contribution of insecticide-impregnated bed nets (ITBN) to malaria control has led to research efforts to determine the impact and sustainability of ITBN programmes in differing environments. There is a need to develop effective, feasible educational strategies that will both inform and motivate community members, and thus maximize the correct usage of ITBN. This is especially true in communities where indigenous usage of bed nets is low. This paper describes the educational component of a randomized controlled community intervention trial of ITBN, with childhood malaria morbidity as an outcome. The educational approach and messages for the ITBN trial were developed from anthropological survey data collected 4 years before the trial, and from community surveys conducted by project researchers. Low levels of understanding amongst mothers of the aetiological link between mosquitos and malaria led to the exclusion of the term 'malaria' from the initial educational messages promoting the use of ITBN. Appropriate individuals within the existing district health care structure were trained as community educators in the project. These educators conducted intensive teaching in the community through public meetings and group teaching in the first 6 months of the trial. The impact of these initial activities was assessed through interviews with a random sample of 100 mothers and 50 household heads. This allowed the identification of messages which had not been well understood and further educational methods were chosen to address the areas pinpointed. The community assessment also demonstrated that, in 1994, over 90% of mothers understood a protective role for bed nets against malaria and the ITBN education messages were changed to take account of this. The school programme was evaluated through determining outreach (the number of households accessed), changes in participant children's knowledge, post-teaching assessment of mothers' knowledge and discussions with parent-teacher associations. It was shown that 40% of intervention homes with children in the target group were accessed, participant children learned the educational messages well (scores increased from a pre-teaching mean of 59% to a post-teaching mean of 92%) and a high level of awareness of the ITBN trial was achieved in these homes (75%). However, specific messages of the education programmed were not well transferred to the home (30%). The discussion emphasises the need for allocation of adequate resources for education in programmes dependent on achieving a change in community practices. We also describe the value of ongoing communication between programme planners and a target population in maximizing the effectiveness of messages and methods used. (+info)
Implementing a nationwide insecticide-impregnated bednet programme in The Gambia.
Earlier studies in The Gambia suggested that the use of impregnated bednets might prove to be a useful malaria control strategy. Based on the results of these studies, in 1992 the Government of The Gambia was encouraged to initiate a National Impregnated Bednet Programme (NIBP) as part of the National Malaria Control Programme Strategy. This paper describes the implementation process/procedure of the NIBP. Evaluation results showed that, overall, 83% of the bednets surveyed has been impregnated, and 77% of children under the age of five years and 78% of women of childbearing age were reported to be sleeping under impregnated bednets. (+info)