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

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.
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PMID:Predicted and observed alleles of Plasmodium falciparum merozoite surface protein-1 (MSP-1), a potential malaria vaccine antigen. 965 29

In a combined retrospective and prospective 4-year study of 6412 children consecutively admitted to St Paul's Hospital, Nchelenge, north-east Zambia, the clinical epidemiology of paediatric disease was described. One diagnosis per admission was noted. Protein-energy malnutrition (PEM) was diagnosed clinically and by means of a modified Wellcome scheme using weight-for-height and Z scores. Correlation coefficients were calculated between monthly admission rates and relative humidity, rainfall and temperature. The age distribution of admitted children showed several distinct groups. Type I (malaria, acute gastro-enteritis, pneumonia and meningitis) had its peak in the 1st 7 months of age, type II (burn wounds and measles) had its main prevalence between the ages of 2 and 4 years, and type III (trauma, typhoid fever, snake bite and tropical ulcer) occurred mainly between 4 and 14 years of age. Admission rates for PEM, PEM subtypes, pneumonia, trauma and snake bite correlated with wet season variables. Malaria and acute gastro-enteritis were extremely common throughout the year. A measles epidemic in the dry season was initially followed by an increase in marasmus, whereas oedematous malnutrition only assumed epidemic proportions associated with a post-measles rise in admission rates of pneumonia. Clinical epidemiological data at the district level is a powerful tool for understanding the pattern of serious paediatric disease in the community.
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PMID:Clinical epidemiology of paediatric disease at Nchelenge, north-east Zambia. 992 74

At the beginning of the 1990s the Chinese Authorities and Rhone-Poulenc Rorer signed an agreement to develop intramuscular (i.m.) artemether (Paluther) and to market the product in the malaria endemic countries. This accord ushered in an exemplary period of co-operation between an international pharmaceutical group and its Chinese partners, the WHO (especially TDR), the Wellcome Trust, and several university research departments. The challenge was to complement the Asian development (to Western standards of Good Manufacturing Practices, Good Laboratory Practices, and Good Clinical Practices) of a molecule which was already used on an everyday basis in East Asia and by Chinese medical missions in Africa. The implementation of Good Manufacturing Practice was the priority for Rhone-Poulenc Rorer in order to ensure the pharmaceutical quality of Paluther. New preclinical and clinical studies confirmed the importance of the drug in the curative treatment of severe malaria due to Plasmodium falciparum, or when resistance to other antimalarial drugs is suspected. The outcome of these new trials was the recognition that i.m. artemether is at least as efficient as quinine. The results of the current development of Paluther have been presented at several international congresses and the latest clinical trials were published in the New England Journal of Medicine in July 1996. The neurotoxicity observed in animals after long term administration of high and repeated dosages has never been reported in human subjects. I.m. artemether was listed in the WHO List of Essential Drugs in December 1995, and the product has now been registered in more than 40 malaria endemic countries. Authorization for use of Paluther in hospitals in France and in several other European countries was granted in 1996.
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PMID:What have been the strategies for the registration, positioning and control of medical information for intramuscular artemether? 1021 6

The 19-kDa conserved C-terminal part of the Plasmodium falciparum merozoite surface protein 1 (PfMSP119) is a malaria vaccine candidate antigen, and human antibody responses to PfMSP119 have been associated with protection against clinical malaria. In this longitudinal study carried out in an area of stable but seasonal malaria transmission with an estimated parasite inoculation of about 20 infective bites/year, we monitored 266 3- to 15-year-old Ghanaian children clinically and parasitologically over a period of 18 months. Blood samples were collected at the beginning of the study before the major malaria season in April and after the season in November. Using enzyme-linked immunosorbent assay, we measured antibody responses to recombinant gluthathione S-transferase-PfMSP119 fusion proteins corresponding to the Wellcome and MAD20 allelic variants in these samples. Prevalence of antibodies recognizing the Wellcome 19 construct containing both epidermal growth factor (EGF)-like motifs in Wellcome type PfMSP119 was about 30%. Prevalence of antibodies to constructs containing only the first EGF domain from either Wellcome or MAD20 type PfMSP119 was about 15%, whereas antibodies recognizing a construct containing only the second EGF domain of MAD20 type PfMSP119 was found in only about 4% of the donors. Neither the prevalence nor the levels of any of the antibody specificities varied significantly with season, age, or sex. Significantly, and in contrast to previous reports from other parts of West Africa, we found no evidence of an association between antibody responses to PfMSP119 and clinical protection against malaria.
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PMID:Levels of antibody to conserved parts of Plasmodium falciparum merozoite surface protein 1 in Ghanaian children are not associated with protection from clinical malaria. 1022 65

Merozoite surface antigen 1 (MSA1) is a promising candidate for vaccine development against malaria parasites. Here, we report the complete nucleotide sequence of the gene encoding the precursor to this major surface antigen of Plasmodium berghei strain ANKA using cDNA library screening and polymerase chain reaction techniques. A single open reading frame of 5,376 basepairs encoding a protein with a calculated molecular mass of 197 kD was defined. The protein contains a putative signal peptide of 19 amino acids, a membrane anchor sequence of 18 residues, and shows two epidermal growth factor-like domains rich in Cys residues at the C-terminus. There are four repeat sequences of oligopeptides in the molecule: tetrapeptide (Ser-Thr-Thr-Thr), tripeptide (Pro-Thr-Pro and Pro-Ala-Ala), and dipeptide (Ser-Gly). Furthermore, three nine-residue stretches of a motif (Ala-Ser-Asn-Pro-Gly-Ala-Ser-Ala-Ser) are located near each other. All of these repeat sequences are unexceptionally located in the variable regions when compared with other MSA1 molecules. The molecule displays 79% overall identity to the analogous antigen of P. yoelii yoelii strain YM, 70% to that of P. chabaudi chabaudi strain AS, and 38% to that of P. falciparum strain Wellcome.
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PMID:Cloning and characterization of the merozoite surface antigen 1 gene of Plasmodium berghei. 1040 33

The Multilateral Initiative on Malaria (MIM) is an international alliance of organisations and individuals. It aims to maximise the impact of scientific research against malaria, through strengthening research capacity in Africa, promoting global collaboration and co-ordination, and increasing available resources. Since its establishment in 1997, the initiative has generated a remarkable level of enthusiasm and activity. Many new scientific partnerships have been established, enabled by enhanced communications and novel funding mechanisms. Dovetailing of research activities with control programmes is also improving. The challenges posed by malaria remain great, however, and in order to achieve a sustainable impact it will be crucial for the research community to capitalise on what has been achieved to date and to maintain the momentum for action well into the next millennium. This article is a personal view contributed by the Wellcome Trust as the nominated co-ordinator for MIM during 1998 and a leading international funder of malaria research. It aims to explain how the novel malaria initiative operates, to summarise some of its key outcomes, and to set out the perspectives for the future.
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PMID:The Multilateral Initiative on Malaria: co-ordination and co-operation in international malaria research. 1069 9

Two clinical trials that used Falcidin (Cosmos Ltd., Nairobi, Kenya), the antifolate combination of pyrimethamine/sulfadoxine (PM/SD), as treatment for non-severe falciparum malaria in children at Kilifi, Kenya in 1987-1988 and 1993-1995 have presented an opportunity to assess in vitro the susceptibility trend of Plasmodium falciparum to PM and SD over time on the Kenya coast. The first set of isolates was collected prior to the introduction of PM/SD into the Kenya Medical Research Institute/Wellcome Trust Research unit while the second set was taken soon after PM/SD was introduced in the study area as the first-line treatment drug for uncomplicated falciparum malaria. In the first trial, 69 isolates collected before and after treatment of malaria with PM/SD were tested directly in the field for susceptibility to PM and SD using the standard in vitro micro-test technique, with minimal levels of folate. In the second trial, 97 isolates similarly collected were adapted to culture, and tested as described elsewhere. In both studies, PM and SD susceptibility tests were done separately. There was a highly significant decrease (P < 0.01) in the in vitro sensitivity of P. falciparum isolates to PM and SD between the two trials. In the first trial, the isolates were either sensitive to both PM and SD or resistant to PM and sensitive to SD. During the second trial, isolates were either resistant to PM and sensitive to SD or resistant to both drugs. These results are important in estimating the useful therapeutic life (UTL) of PM/SD in this area and in identifying alternative antifolate drugs.
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PMID:The changing in vitro susceptibility pattern to pyrimethamine/sulfadoxine in Plasmodium falciparum field isolates from Kilifi, Kenya. 1103 85

The Mapping Malaria Risk in Africa (MARA) project will use computerized geographic information systems (GIS) to create an atlas of malaria risk in Africa. This is the first time GIS will be used to predict such risk and the first attempt to map malaria risk on a continental scale. Many heterogenous data sets relevant to the transmission dynamics of the disease will be combined, including the manipulation of the climatic factors which affect vector distribution and malaria transmission into a new index of malaria risk, and its validation against actual data. Specifically, the MARA project will collate measures of malaria risk, mainly the parasite ratio and annual incidence, to obtain an index for Africa and to create a continental, spatial, and temporal database. Five planned regional centers will work with a coordinating center in Durban, South Africa. The effort recently received its first funding. Canada's International Development Research Center, the World Health Organization/TDR bednet task force, the Wellcome Trust, and the South African Medical Research Council are supporting the effort.
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PMID:An atlas of malaria in Africa. 1229 3

New Medicines for Malaria Venture (MMV) is a public/private, nonprofit initiative to develop 1 new drug against malaria every 5 years. It will operate under the umbrella of Roll Back Malaria, a new project launched by World Health Organization (WHO) Director General, Dr. Gro Harlem Brundtland. The UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases (TDR) helped establish the MMV through its product R&D unit, and there has been considerable industrial input. The World Bank and the Global Forum for Health Research are other international agencies involved in the initiative, while several philanthropic organizations such as the Rockefeller Foundation and the Wellcome Trust have also played major roles. MMV will create a fund and operate by financing and resourcing a limited number of projects in a manner compatible with industrial procedures. The fund is mainly supported financially by the public sector, while a funding commitment of US$15 million/year rising to US$30 million a year is being sought. Companies are providing mainly in-kind support.
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PMID:MMV: New Medicines for Malaria Venture. 1232 22

In 1996, Glaxo Wellcome offered to donate up to a million treatment courses annually of Malarone, a new antimalarial, with a view to reducing the global burden of malaria. The Malarone Donation Programme (MDP) was established the following year. Eight pilot sites were selected in Kenya and Uganda to develop and evaluate an effective, locally sustainable donation strategy that ensured controlled and appropriate use of Malarone. The pilot programme targeted individuals who had acute uncomplicated Plasmodium falciparum malaria that had not responded to first-line treatments with chloroquine or sulfadoxine-pyrimethamine. Of the 161 079 patients clinically diagnosed at the pilot sites as having malaria, 1101 (0.68%) met all the conditions for participation and received directly observed treatment with Malarone. MDP had a positive effect at the pilot sites by improving the diagnosis and management of malaria. However, the provision of Malarone as a second-line drug at the district hospital level was not an efficient and effective use of resources. The number of deaths among children and adults ineligible for MDP at the pilot sites suggested that high priority should be given to meeting the challenges of malaria treatment at the community level.
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PMID:A public-private partnership for malaria control: lessons from the Malarone Donation Programme. 1247 3


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