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)

Three octapeptides from the N and C terminal C regions of the merozoite surface Ag 2 (MSA2) of Plasmodium falciparum elicit anti-MSA2 antibody when given as diphtheria toxoid conjugates. These antibodies also bind to the MSA2 homolog from the rodent malaria Plasmodium berghei. All mice vaccinated with these conjugates and challenged with an otherwise lethal inoculum of P. berghei showed substantial protection with most surviving. There was a inverse correlation between the development of the parasitemia and the antibody titer, with alum, algammulin, and CFA giving comparable results. These observations show that the conserved region of MSA2 could form the basis of a malaria vaccine when presented in a suitably immunogenic form, thus avoiding the problems of antigenic diversity [corrected].
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PMID:Protective immunization with invariant peptides of the Plasmodium falciparum antigen MSA2. 172 67

An effective malaria vaccine must be capable of eliciting a protective immune response in individuals of diverse genetic makeup. In this report, we describe the co-regulation of immune responsiveness to growth-inhibitory Plasmodium falciparum merozoite surface protein-1 (MSP-1) epitopes by MHC-linked immune response genes and by the adjuvant used in MSP-1 vaccine formulations. When congenic mice differing in MHC haplotype were immunized with MSP-1 either in CFA or incorporated into a synthetic monophosphoryl lipid A (LA-15-PH)-liposome formulation, mice of different haplotypes produced anti-MSP-1 Abs capable of inhibiting P. falciparum growth. Mice of H-2b and H-2ja haplotypes produced Abs possessing high levels of inhibitory activity upon immunization with MSP-1 in LA-15-PH/liposomes whereas these haplotypes produced noninhibitory Abs when immunized with MSP-1 in CFA. Conversely, H-2d haplotype mice produced inhibitory Abs when immunized with MSP-1 in CFA but not when immunized with MSP-1 in LA-15-PH/liposomes. The LA-15-PH/liposome adjuvant was more effective than CFA in inducing growth-inhibitory Abs. The level of parasite growth inhibition observed for a particular mouse strain correlated with Ab titers against conserved, C-terminal MSP-1 epitopes, which appear to be important targets for Ab-mediated inhibition in mice immunized with both adjuvant formulations. Our results suggest that adjuvant formulation and MHC genes act in a reciprocal manner to control immune responsiveness to specific epitopes, and raise the possibility of manipulating genetically-controlled responsiveness to vaccine Ags by utilizing alternative adjuvants in vaccine formulations.
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PMID:Regulation of antibody specificity to Plasmodium falciparum merozoite surface protein-1 by adjuvant and MHC haplotype. 814 29

Immunisation with two chemically synthesised, linear, multiple epitope peptides (MEP) containing B and T cell epitopes from two conserved blood-stage antigens of the human malaria parasite, Plasmodium falciparum, induced high levels of circulating antibodies without the use of a carrier protein. Immunisation of BALB/c mice with MEP constructs (P1 and P2) induced antibodies against the various epitope sequences included in their structures, although the immune response was focused more towards the N terminal and the middle portion of the peptides. In vitro T cell proliferation assays indicated that only one of the two Th epitopes included in P1 and P2 are functional. Both P1 and P2, based on P. falciparum sequences, cross-reacted with sera from P. yoelii-infected mice. Immunisation with P1 in CFA, but not with P2, provided partial protection to BALB/c mice against P. yoelii challenge infection. Peptide P1 was highly immunogenic in alum also, and a somewhat higher level of protection was observed as compared to CFA immunisation. We found that immunisation with P1 induced antibody responses in different strains of mice, although to different extents. These results suggest that linear, multiple epitope peptides may offer attractive alternatives as subunit vaccine candidate molecules, but at the same time highlight the fact that the design principles are far from being clear and have yet to be worked out.
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PMID:Fine specificity of immune responses to epitopic sequences in synthetic peptides containing B and T epitopes from the conserved Plasmodium falciparum blood-stage antigens. 857 29

To optimize the funds devoted to health care, and to objectively assess the tools used in monitoring patients with cerebral malaria, we determined two parameters, care charges and direct costs due to hospitalization. During this longitudinal study conducted at the Albert Royer Pediatric Hospital in Dakar from October 15, 1991 to October 15, 1992 with 76 cases, malaria represented 5.2% of the febrile cases and 3.4% of the hospitalized cases. The lethality rate was 3.4%. Clinical features were not correlated with care charges and thus were not good indicators of worker's labor. The average cost of a cerebral malaria hospitalization was estimated at 35,710 F CFA (In October 1992, 1 F CFA = 0.02 FF). This cost is very high depending the limited resources of the region. Rapid and proper treatment of malaria cases may lead to a significant reduction of costs.
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PMID:[Care charges and direct costs related to hospitalization of Senegalese children with cerebral malaria. Study of 76 cases in the Albert-Royer Hospital in Dakar in 1991-1992]. 877 46

Variable protection against malaria blood-stage infection has been demonstrated in mice following parenteral immunization with the highly conserved 19 kD carboxylterminal fragment of the merozoite surface protein-1 (MSP119) using CFA/IFA and other adjuvants. Here we show that intranasal immunization of BALB/C mice with yeast expressed Plasmodium yoelii MSP119 plus a mixture of native and recombinant cholera toxin B subunit, could induce serum MSP119-specific antibodies at titres ranging from 20 000 to 2 560 000. The Ig subclass responses were predominantly G1 and G2b. Intranasal immunization led to protection following challenge (peak parasitaemia < 1%) in mice with the highest MSP119-specific titre (>/= 640 000). In two of the three protected mice, a peak parasitaemia of 0.1%-1% was followed by a boost of the antibody response whereas one of the three protected mice did not boost its antibody response after a peak parasitaemia of 0.02%. In unprotected mice, antibody levels rose, then fell, following the detection of parasites in the peripheral blood. CD4+ T cell-depletion abrogated the ability of the mice to boost their antibody response following challenge. These data demonstrate the potential for intranasal immunization with MSP119 to protect against malaria.
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PMID:Intranasal immunization with yeast-expressed 19 kD carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (yMSP119) induces protective immunity to blood stage malaria infection in mice. 976 8

This prospective one-year study was conducted as a preliminary phase to setting up a protocol for economic appraisal of management of severe malaria at Albert Royer Children's Hospital in Dakar, Senegal. Data was routinely collected using a standardized checklist. The four key indicators chosen for this study were nurse workload, adequacy of care (number of patients receiving adequate care), direct cost, and mortality rate. The mean daily care workload was estimated to be 27.2 minutes. This indicator assesses the relationship between supply and demand. Based on 5 criteria, care was considered as adequate in 54.5 p. 100 of patients. This indicator is helpful in judging the effectiveness of the therapeutic modalities used. The direct cost of treating severe malaria was estimated to be 45963 CFA francs. This indicator will be useful in establishing controls to reduce costs. The mortality rate was 12.2 p. 100. Comparison of this rate with previous years suggests little improvement in the outcome of malaria management at the institution. This indicator must be taken into account in the ongoing quality control program. Overall these findings should enable institutional decision-making to improve management of severe malaria based on objective measurable data.
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PMID:[Management of severe malaria in children in developing countries. A protocol for economic evaluation]. 1070 Dec 9

After 1977 the world's economic situation deteriorated, and by the 1980's Africa's standard of living was the lowest in the world: 2.3% lower than the region's population growth rate. The economic crisis and structural adjustment policies (SAP) have had a negative influence on the development of health care in Africa. The health sector in all African countries have the lowest budgets and these meager budgets were further cut with the SAP. The WHO stated that of 21 Ministries of Health surveyed in 1987, only 3 had a health budget over 9% with the remaining 18 between 2-8%; by 1986-87 and as a result of SAP it became 2.4%. Such a decline affected the availability and accessibility of health care, medicines, transportation, and health personnel. The lack of resources and manpower promoted the onset of epidemics such as cholera and diarrhea. Rural migration to the cities has aggravated promiscuity and exacerbated contagious diseases like tuberculosis and malaria. The victims of SAP are generally women and children. The economic crisis facing Africa is so devastating that families can no longer afford to pay for gas, hospitalization and medication when they are ill. African women are the ones responsible for the health status of the family, including their nutrition. The negative effects of the SAP on women are being felt in their levels of malnutrition, lack of prenatal care, and deliveries without health personnel. Zambia's infant and child mortality rate (1-14) has grown from 27-47%, while Burkina Faso and Chad have IMR's of over 200/1000 live births. The health status of children are equally aggravated by war and famine. In spite of all these obstacles, Senegal is trying to overcome the problems through community action. In 1985 the health committees contributed more than 386 million CFA to build health facilities and provide medications to the community. Between 24-70% of all health care is covered by donor assistance in Africa.
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PMID:[Interview of Doctor Monekosso: structural adjustment --a medication that is making us ill]. 1228 83

The Emergency Department, the showcase of the hospital, must be functional at all times with sufficient resources for looking after the patients without delay. In the Medical Emergency Department of the Yalgado Ouedraogo national hospital of Ouagadougou (Burkina Faso), problems such as delays and difficulties to obtain medicine, give rise to conflicts thus causing the hospital to be a target for public criticism. The aim of this study is to establish the profile of the patients and to assess how they are taken care of. A cross-sectional survey was carried out for 21 consecutive days spread out over three months, from April 25 to June 25, 1997 and concerned all of the 551 patients consulting on those days. The self referral rate was 50.8%. Patients came mainly from the Kadiogo province (90.7%), with their own transport means (85.1%), more often at the beginning of the week (31 patients per day on average) than during week ends (21 patients per day on average, p<0.001). The age group was 15 to 93 years with a mean of 35.4 ( 14,2) years. Infectious diseases, particularly gastroenteritis (21.3%), malaria (12.1%), and pneumonia (10.2%) were the main diagnoses. The median waiting time was 8 min (from 0 to 3 h 59 min), the median therapeutic time was 56 min (from 5 min to 16 h 19 min). Patients were supplied with medicine in 14.5% of cases. Thus median medicine acquisition time was significantly reduced from 35 min to 21 min (p<0.001) when medicines were bought. Medicine acquisition time significantly contributes to increase the therapeutic delay (rs=0.31; p<0.001). The median therapeutic time was 56 min (5 min to 16 h 19 min). The diagnostic accuracy rate was 77.4%, and the satisfaction index 3.5%. Patients expenditure was 9,002 CFA francs on average, including 7,963 CFA francs for medicine. Thus access to medicine constitutes a major point of malfunction, increasing the caretaking time span as well as patients' expenditure. In addition to quickly and systematically supplying medicines to all patients, organizing the reception and providing comfortable waiting conditions must be considered in order to offer better care delivery services.
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PMID:[Medical emergencies in the Yalgado Ouedraogo national hospital of Ouagadougou: patients' profile and assessment of care practices]. 1247 25

The 19kDa carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (MSP1(19)), an analog of the leading falciparum malaria vaccine candidate, induces protective immunity to challenge infection when formulated with complete/incomplete Freund's adjuvant (CFA/IFA), an adjuvant unsuitable for use in humans. In this study, we investigate Montanide ISA51 and Montanide ISA720 as well as CpG oligodeoxynucleotide (ODN) as adjuvants for induction of immunity to MSP1(19). Mice immunized with MSP1(19) adjuvanted with Montanide ISA51 were protected even though some mice experienced low-grade parasitemia before resolving the infection. Mice immunized with MSP1(19) adjuvanted with Montanide ISA720 showed delayed patent parasitemia with all mice ultimately succumbing to infection. Interestingly, when the synthetic CpG ODN 1826 was included in either Montanide formulation, mice were completely protected with no parasites detected in the blood. MSP1(19)-specific antibodies in MSP1(19)-immunized mice adjuvanted with Montanide ISA51 or Montanide ISA720 showed predominantly IgG1 antibody and low levels of IgG2a. CpG ODN 1826 significantly enhanced both IgG1 and IgG2a antibody responses in Montanide ISA51-adjuvanted mice but significantly enhanced only the IgG2a antibody response in Montanide ISA720-adjuvanted mice. To investigate the relative roles of antibody and CD4(+) T cells in protection, MSP1(19)-immunized mice adjuvanted with Montanide ISA720 and CpG ODN 1826 were depleted of CD4(+) T cells just prior to challenge. Results showed that three of nine immunized/T cell depleted mice died following infection. These results suggest that antibody and CD4(+) T cells are critical for protection following immunization with MSP1(19) adjuvanted with Montanide and CpG ODN and that the formulation of a human malaria vaccine candidate in Montanide ISA720 or ISA51 together with human compatible CpG ODN would be useful for improving efficacy.
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PMID:CpG oligodeoxynucleotide enhances immunity against blood-stage malaria infection in mice parenterally immunized with a yeast-expressed 19 kDa carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (MSP1(19)) formulated in oil-based Montanides. 1279 36

Unmethylated CpG dinucleotide motifs present in bacterial genomes or synthetic oligodeoxynucleotides (ODNs) serve as strong immunostimulatory agents in mice, monkeys and humans. We determined the adjuvant effect of murine CpG ODN 1826 on the immunogenicity and protective efficacy of the Saccharomyces cerevisiae-expressed 19-kDa C-terminal region of merozoite surface protein 1 (yMSP1(19)) of the murine malaria parasite Plasmodium yoelii. We found that in C57BL/6 mice, following sporozoite challenge, the degree of protective immunity against malaria induced by yMSP1(19) in a formulation of Montanide ISA 51 (ISA) plus CpG ODN 1826 was similar or superior to that conferred by yMSP1(19) emulsified in complete Freund's adjuvant (CFA/incomplete Freund's adjuvant). In total, among mice immunized with yMSP1(19), 22 of 32 (68.7%) with ISA plus CpG 1826, 0 of 4 (0%) with CFA/incomplete Freund's adjuvant, 0 of 4 (0%) with CpG 1826 mixed with ISA (no yMSP1(19)), and 0 of 11 (0%) with CpG 1826 alone were completely protected against development of erythrocytic stage infection after sporozoite challenge. The adjuvant effect of CpG ODN 1826 was manifested as both significantly improved complete protection from malaria (defined as the absence of detectable erythrocytic form parasites) (P = 0.007, chi square) and reduced parasite burden in infected mice. In vivo depletions of interleukin-12 and gamma interferon cytokines and CD4+ and CD8+ T cells in vaccinated mice had no significant effect on immunity. On the other hand, immunoglobulin G (IgG) isotype levels appeared to correlate with protection. Inclusion of CpG ODN 1826 in the yMSP1(19) plus ISA vaccine contributed towards the induction of higher levels of IgG2a and IgG2b (Th1 type) antibodies, suggesting that CpG ODN 1826 caused a shift towards a Th1 type of immune response that could be responsible for the higher degree of protective immunity. Our results indicate that this potent adjuvant formulation should be further evaluated for use in clinical trials of recombinant malarial vaccine candidates.
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PMID:CpG oligodeoxynucleotide and Montanide ISA 51 adjuvant combination enhanced the protective efficacy of a subunit malaria vaccine. 1474 40


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