Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As part of a multi-disciplinary research programme undertaken by the Papua New Guinea Institute of Medical Research near the town of Madang, northern PNG, a three-year study of mortality was conducted in a rural population of approximately 16,500 people. From early 1982 the area was under continuous demographic surveillance which continued for the three years of the study. All deaths which occurred in this period were investigated by interviewing relatives of the deceased and examining any available health service records. Respiratory diseases were the commonest cause of death, with pneumonia accounting for 20% of deaths in children under 10 years of age, and pneumonia and chronic obstructive lung disease (COLD) together accounting for a third of all deaths. Deaths from COLD were more common in the study population than in PNG hospitals and health centres. The proportion of deaths caused by malaria in children under 10 years was estimated to be between 4 and 17%. Mortality rate in the first year of life were determined by following up a cohort of 1015 births occurring in the first 20 months of the study. Of the 1002 live births, 46 died in the first 12 months of life, giving an infant mortality rate of 45.9% live births. Other mortality and demographic rates were consistent with data reported from the 1980 PNG National Census, suggesting that the study population belonged to an advantaged rural area. Demographic features found in this population were a high birth rate, a relatively low crude death rate, and a rate of natural population increase of 2.8% per annum. The methodological difficulties associated with the measurement of malaria mortality have important implications for the evaluation of future malaria vaccines. The methods employed in this study are critically discussed, and recommendations made for future studies.
 ...
PMID:Mortality in a rural area of Madang Province, Papua New Guinea. 260 69

Differential screening of cDNA libraries constructed from knobby and predominantly knobless Plasmodium falciparum isolates, identified the sequence SD17. Chromosome blotting experiments have shown that this sequence, which is located on chromosome 2 of most isolates, was deleted in the cloned parasite line E12 of the FCQ27/PNG isolate. Here we show that erythrocytes infected with the SD17-containing cloned line D10 have typical knob structures on their surfaces, whereas those infected with the line E12 lack knobs. An expression clone was constructed from SD17 and used to affinity purify antibodies from the sera of individuals living in areas of Papua New Guinea where malaria is endemic. The antibodies reacted in immunoblotting experiments with a single polypeptide that varied in Mr from 85,000 to 105,000 among different isolates. The antigen was not expressed in the knobless clone E12. Postembedding immunoelectron microscopy showed localization of the antigen over the knobs of FC27 and two other isolates, largely on the cytoplasmic side. We conclude that the parasite antigen corresponding to clone SD17 is a knob protein.
 ...
PMID:Plasmodium falciparum: identification and localization of a knob protein antigen expressed by a cDNA clone. 354 49

As part of a multi-disciplinary malaria research programme in a rural area of Madang Province, the Papua New Guinea Institute of Medical Research (PNG IMR) in 1982 established a village-based intervention programme of presumptive treatment of fever in 35 villages (population about 5,200). Seventy-four villages aides, selected by people from their own village, attended two-week training courses conducted by PNG IMR staff, and were trained to dispense three-day courses of amodiaquine (for children) or chloroquine (for adults) to anyone presenting with fever (presumptive malaria). The majority of village aides, who were voluntary workers, were married men and women between the ages of 20 and 35 years, who had had up to six years' schooling. In 1983, 5,075 fever cases were treated by village aides, which represents a quarter of the number of fever episodes estimated to occur each year in this area. Utilization of village-aide services was variable, the most important determining factors being the personality and standing of the village aide, and the distance (walking time) to the village aide's house from the patient's house. The village aides' role was expanded to include taking blood slides, dispensing other medicines (aspirin and dressings), treatment of diarrhoea by oral rehydration, and registration of vital demographic events in the village. Regular supervision, currently undertaken on a two-weekly basis by PNG IMR staff, regular refresher courses, and, probably, some sort of compensation (not necessarily monetary) are important for the long-term continuation of the programme, which may serve as a model for other areas.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The role of voluntary village aides in the control of malaria by presumptive treatment of fever. 1. Selection, training and practice. 386 59

A village-based programme of presumptive treatment of fever, using voluntary village aides to dispense oral chloroquine or amodiaquine, was established in 1982 by the Papua New Guinea Institute of Medical Research (PNG IMR) in 35 rural villages or hamlets near Madang, on the north coast of PNG. In the course of the following two years, village aides became an established health resource in many of those villages, although in others they were poorly utilized. In attempting to evaluate the impact of the programme on village health, a number of parameters were investigated. These included malaria-related mortality and morbidity, and the prevalence of parasitaemia and splenic enlargement in children in the study area. Deaths attributable to malaria, which accounted for 11% of deaths in the under-10 year age-group, and cerebral malaria cases were too few to be useful as parameters to evaluate the programme. No reduction in spleen or parasite rates occurred in children as a result of the village aide programme. In two villages, there was an unexplained increase in spleen rate following the introduction of a village aide. A study of malaria-related morbidity, by investigation of all fever cases occurring in a two-week recall period, was conducted in mid-1984. House-to-house interviews were carried out in 19 villages: 9 control villages, where there was no village aide, 6 where the village aide was well utilized, and 4 where the village aide was poorly utilized. The study showed that village aides had a measurable impact on morbidity due to fever in villages where they were well utilized, primarily by reducing the duration of fever through early treatment. The results also suggested that children benefitted even in the villages where the overall utilization of village aides was low. It is felt that such a programme would have had an even greater impact in areas where access to existing health services is more difficult than in the study area.
 ...
PMID:The role of voluntary village aides in the control of malaria by presumptive treatment of fever. 2. Impact on village health. 386 60

We describe a procedure that uses polyspecific human sera for screening Escherichia coli colonies expressing cloned Plasmodium falciparum cDNA sequences in order to detect colonies that react differentially with different sera. This procedure can be used for two distinct purposes. First, it enables the isolation of clones encoding specified antigenic sequences present in the complex mixture, without purification of either antigens or antibodies by conventional procedures. This requires that the antigen can be expressed in E. coli and that antisera are available that differ substantially in their reactivities to the component of interest. To develop the procedure, we used two polyspecific sera that shared many anti-P. falciparum specificities but differed in that only one was reactive to the isolate-specific S antigen of P. falciparum strain FCQ27/PNG (called FC27). Differential screening with the two sera identified 30 cDNA clones, and colony hybridization confirmed that 25 of these express S-antigen sequences. Second, the procedure identifies defined antibody specificities within polyspecific human sera by virtue of their ability to react with any given cDNA clone. The procedure has been used here to identify antibody specificities that increase dramatically in titer between the acute and convalescent phases of malaria in certain individuals and, hence, to isolate clones encoding the corresponding antigens.
 ...
PMID:Differential antibody screening of cloned Plasmodium falciparum sequences expressed in Escherichia coli: procedure for isolation of defined antigens and analysis of human antisera. 637 14

A library of cDNA clones expressing antigens of the asexual blood-stages of Plasmodium falciparum (isolate FCQ27/PNG) was constructed in the bacteriophage vector gamma gt11-Amp3. Clones expressing P. falciparum antigens (as polypeptides fused to beta-galactosidase) were selected by their reactivity in an in situ colony immunoassay with affinity-purified malaria antibodies. A detailed analysis of 78 antigen-positive clones selected from approximately 10,000 recombinant clones has shown them to correspond to many different parasite antigens. cDNA hybridization studies on this array of 78 antigen-positive clones have so far identified 18 families of sibling clones with 22 clones as yet unassigned, the majority of which may represent additional unique sequences. Only about 20% of the clones synthesized abundant amounts of the malaria antigen/beta-galactosidase fused polypeptide but each multi-member family except one was represented by at least one clone producing a fused polypeptide in abundance. Antisera have been raised against cloned malaria antigens by immunizing mice and rabbits with bacterial lysates and purified fused polypeptides, respectively. These antisera have been used to characterize the antigens in P. falciparum that correspond to the various antigen-positive clones. The variety of distinct antigens recognized by these antisera confirms that the clone library contains coding sequences for many different antigens.
 ...
PMID:Plasmodium falciparum complementary DNA clones expressed in Escherichia coli encode many distinct antigens. 639 47

Recent work has suggested that important B- and T-cell epitopes on the circumsporozoite protein (CSP) of Plasmodium vivax lie external to the major repeat regions of the protein. We have studied two naturally exposed human populations (Caucasian and Papua New Guineans) and determined the antibody response to yeast-derived recombinant CSPs, overlapping synthetic peptides spanning amino acids 76 348 of the Belem P. vivax CSP and overlapping peptides representing the variant repeats of the VK247 strain of P. vivax. We have demonstrated that the P. vivax CSP-specific antibody response is directed towards areas within the repeat region as well as areas external to this; but the dominant epitopes recognized by the two populations studied, were distinct. One epitope, lying external to the repeats and recognized by both populations, partially overlaps an area of the protein referred to as region II-plus. Sera from malaria-exposed Papua New Guineans and Thais contained antibodies to this epitope (V22, single letter amino acid sequence TCGVGVRVRRRVNAANKKPE) which were capable of recognizing sporozoites, as determined by quantitative inhibition IFA. Seventeen percent of PNG sera had antibodies to this peptide compared with 33% who had antibodies to the central repeats of the protein. Immunization of mice with recombinant CSP did not induce antibodies to V22. However, immunization with overlapping peptide epitopes representing this region (V21 or V22) induced specific antibodies but only two sera recognized both V21 and V22 and, by inference, the overlapping peptide sequence (TCGVGVRVRR). Antibodies in these two sera could bind recombinant CSP in ELISA; however, in contrast, nine sera which recognized either V21 or V22 alone did not bind CSP. Only one of two sera containing antibodies recognizing CSP stained P. vivax sporozoites. This serum also recognized an epitope dependent upon two amino acids aminoterminal to V22. These data suggest that the fine specificity of antibodies is a critical determinant for binding to both recCSP and sporozoites.
 ...
PMID:Fine epitope specificity of antibodies to region II of the Plasmodium vivax circumsporozoite protein correlates with ability to bind recombinant protein and sporozoites. 916 1

The 19-kDa antigenic domain of Plasmodium falciparum merozoite surface protein (MSP)-1 is a potential malaria vaccine candidate. Based on the amino acid substitution, four known alleles, E-TSR (PNG-MAD20 type), E-KNG (Uganda-PA type), Q-KNG (Wellcome type), and Q-TSR (Indo type) of this domain have been identified. Using single or double crossover recombinational events, we predicted the existence of additional alleles of this antigen. The presence of the predicted alleles was determined in parasite isolates from western Kenya, by undertaking a cross-sectional and a longitudinal study. Of the ten predicted alleles, we have revealed the presence of three new alleles: E-KSG-L (Kenya-1 type); E-KSR-L (Kenya-2 type); and E-KNG-F (Kenya-3 type). The results of this study suggest that it may be possible to predict the complexity of the genetic makeup of natural parasite populations.
 ...
PMID:Predicted and observed alleles of Plasmodium falciparum merozoite surface protein-1 (MSP-1), a potential malaria vaccine antigen. 965 29

The genetic diversity of P. falciparum and multiplicity of infection has been studied in a village in Northern Nigeria at the end of the rainy season, when transmission is high. We analysed blood samples from 104 individuals aged 5-70 years by polymerase chain reaction (PCR) amplifying the gene for the merozoite surface protein MSP2 followed by genotyping based on restriction fragment length polymorphism (RFLP). 94.2% of all samples were parasite positive by PCR and over 80% of those had multiple infections. The age distribution of the average number of parasite clones present in P. falciparum infections showed an initial increase, then reached a peak multiplicity in children 8-10 years of age, and afterwards decreased significantly with age. Mean multiplicity in those 8-10-year-old children was 5.4 clones per carrier. Peak multiplicity and parasite diversity in Nigerian individuals is compared to findings from other study sites in Africa and PNG. The prevalence of IgG antibodies against the circumsporozoite protein (CSP), an indicator for malaria exposure, was over 85% in all age groups showing a high exposure of villagers to P. falciparum. OD values in ELISA were positively correlated with age. There was no correlation between the level of IgG against CSP and the multiplicity of P. falciparum infections determined by PCR of msp2. These results imply that in highly endemic areas multiplicity of infection is not directly correlated with exposure to P. falciparum.
 ...
PMID:Analysis of Plasmodium falciparum infections in a village community in Northern Nigeria: determination of msp2 genotypes and parasite-specific IgG responses. 1064 9

The Papua New Guinea Institute of Medical Research (PNGIMR) is one of the most respected health research institutions in the developing world, and its studies of the local health problems of PNG have consistently had international relevance. This article examines the structural and philosophical factors that have enabled the success of the PNGIMR, and presents the PNGIMR approach to research as a potential model for other disease-endemic countries. An overview of PNGIMR research into malaria and filariasis is given with selected examples as an introduction to a Trends in Parasitology series on health research in Papua New Guinea.
 ...
PMID:Health research in Papua New Guinea. 1279 79


1 2 Next >>