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 functional properties, regarding parasite growth inhibition in vitro, the cytotoxic potential and cytokine profiles of human gammadelta+ and alphabeta+ T cells, T-cell lines and clones stimulated with Plasmodium falciparum-antigen-or T-cell mitogen in vitro were investigated. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and specific primers, mRNA for the cytolytic molecules perforin, granzyme A and B, Fas and Fas ligand (FasL) were detected in both the gammadelta- and the alphabetaT cells. Despite this fact, only gammadeltaT cells inhibited, both Vdelta1+ and Vdelta2+, the in vitro growth of the asexual blood stages in a dose dependent manner. The inhibition required cell-to-cell contact and was not observed until the second parasite replication implied that the likely gammadeltaT-cell target was the extracellular merozoite or schizont. The failure of alphabetaT cells to inhibit the growth of the parasite suggests requirement of additional cytolytic molecules/signals or different receptor specificities exhibited by the gammadeltaT cells. Both the gammadelta- and alphabetaT cells expressed mRNA for a large number of cytokines. Interferon (IFN)-gamma, interleukin (IL) IL-5, IL-6, IL-8, tumour necrosis factor alpha (TNFalpha), tumour necrosis factor beta (TNF-beta)/lymphotoxin (LT) and T-cell growth factor beta-1 (TGF-beta1) were observed in all activated clones tested. No IL-3 was detected, while IL-1beta, IL-2, IL-4, IL-10 and GM-CSF were variably expressed. In conclusion, our data show that gammadeltaT cells in malaria nonimmune individuals inhibit the asexual blood stages of P. falciparum malaria, while similarly activated alphabetaT cells do not. Thus, it is likely that the gammadeltaT cells could play a mandatory role in the elimination of parasites and/or the regulation of the early immune response to malaria infection.
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PMID:Human gamma delta T cells that inhibit the in vitro growth of the asexual blood stages of the Plasmodium falciparum parasite express cytolytic and proinflammatory molecules. 1060 13

Of 51 consecutive children with cerebral malaria, fever, convulsions, and drowsiness were the commonest presenting symptoms. Decerebrate and decorticate postures and absent cornea reflex were the commonest brain stem signs. Opening lumbar cerebrospinal (CSF) pressure was raised in all but one of 24 children in whom it was reliably measured [mean 15.2 +/- 5.7 mmHg, range 6-24]. Hyponatraemia occurred in 17 (33%). Acute renal failure was not uncommon; the combination of hypercreatininaemia (plasma creatinine > 100 mumol/L) and hyperkalaemia (plasma potassium > 6.0 mumol/L) was fatal in 5 out of 7 patients in whom it occurred. Disturbances of acid-base status were present in all 40 children in whom it was assessed on admission. Mortality rate was 16% (8 patients). Neurological deficits occurred in 7 (14%) of the survivors and included cortical blindness [3], aphasia [3], hypertonia [3], hearing loss [2], and dystonia [1]. In addition to the present measures aimed at reducing morbidity and morality in children with cerebral malaria, efforts should be directed at rapid assessment of renal function and prompt correction of such dysfunction if found.
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PMID:Clinical study of cerebral malaria in African children. 1089 20

Sixty patients of inflammatory brain disease were diagnosed and classified according to clinico-investigational criteria by Ahuja et al into tuberculous meningitis group (36 patients) and non-tuberculous meningitis group (24 patients). Tuberculous meningitis (TBM) patients were classified as probable (9 patients) and possible (27 patients) TBM. Non-TBM group comprised of pyogenic meningitis (8.3%), viral encephalitis (23.3%), cerebral malaria (5%) and enteric encephalopathy (3.3%). Cerebrospinal fluid-adenosine deaminase (CSF-ADA) activities were measured in both TBM and non-TBM groups. Mean CSF-ADA levels in TBM patients was 9.61 +/- 4.10 IU/L and was significantly elevated as compared to viral encephalitis and enteric encephalopathy cases; but difference was insignificant in comparison to pyogenic meningitis (7.92 +/- 0.95 IU/L) and cerebral malaria. Using 8 IU/L as cut off value for diagnosis of TBM a sensitivity of 44% and specificity of 75% was observed.
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PMID:Evaluation of CSF-adenosine deaminase activity in tubercular meningitis. 1099 88

MuStDO 5 is a multivalent plasmid DNA vaccine for malaria comprised of five plasmid DNAs encoding five proteins from Plasmodium falciparum and one plasmid DNA encoding human GM-CSF. To evaluate the safety of MuStDO 5, a series of pre-clinical studies were conducted in mice and rabbits. In pharmacology studies in mice, GM-CSF could not be detected in the serum following either intramuscular or a combined intramuscular/intradermal administration of the vaccine, but was readily detected in the muscle following intramuscular administration. In a tissue distribution study in mice, MuStDO 5 plasmid DNA was detected by PCR initially in highly vascularized tissues, while at later time-points the plasmid DNA was detected primarily at the site(s) of injection. In GLP safety studies in mice and rabbits, repeated intramuscular/intradermal administration of the MuStDO 5 vaccine was found to be safe and well tolerated without any evidence of autoimmune pathology.
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PMID:Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine. 1143 36

Two chimpanzees were vaccinated intramuscularly against malaria using plasmid DNA expressing the pre-erythrocytic antigens thrombospondin related adhesion protein (PfTRAP) and liver stage specific antigen-1 (PfLSA-1) of Plasmodium falciparum together with GM-CSF protein. A recombinant modified vaccinia virus Ankara (MVA) expressing PfTRAP was injected intramuscularly 6 weeks later to boost the immune response. This sequence of antigen delivery induced a specific and long-lasting T cell and antibody response to PfTRAP as detected by ELISPOT assay and ELISA. Antibody responses were detected after four DNA injections, and were boosted by injection of recombinant MVA expressing PfTRAP. Interferon-gamma secreting antigen-specific T cells were detected in both animals, but only after boosting with recombinant MVA. By screening a panel of PfTRAP-derived peptides, an epitope was identified that was recognized by cytotoxic T lymphocytes in one of the chimpanzees studied. T cells specific for this epitope were present in PBMCs and liver-infiltrating lymphocytes at a frequency of between 1 in 200 and 1 in 500. The high immunogenicity of this prime-boost regimen in chimpanzees supports further assessment of this delivery strategy for the induction of protection against P. falciparum malaria in humans.
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PMID:A prime-boost immunisation regimen using DNA followed by recombinant modified vaccinia virus Ankara induces strong cellular immune responses against the Plasmodium falciparum TRAP antigen in chimpanzees. 1153 6

Nitrate levels in CSF and sera from 16 coma and 19 noncoma falciparum malaria patients were determined using nitric oxide colorometric assay. The medians (range lower, upper limits) of nitrate in sera of comatose and noncomatose patients were 0.28 (0.11, 1.24) and 0.23 (0.05, 0.87) microM, respectively. The medians of nitrate level in CSF of coma and noncoma cases were 0.09 (0.01, 0.28) and 0.15 (0, 1.18) microM, respectively. There was no difference of nitrate level in sera and CSF from comatose or noncomatose patients compared to that in normal sera and CSF. The amount of nitrate in sera and CSF of both groups was not significantly correlated with coma depth, parasitemia, parasite clearance time and time to recovery. Contrast to our in vitro study using immunoperoxidase staining, we found inducible nitric oside synthase production by brain endothelial cells during 4-24 hours of coculturing with late stage of P. falciparum infected red blood cells. These results suggests that malaria severity can not be differentiated by nitrate level in body fluid.
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PMID:Lack of association between CSF nitrate and sera nitrate in falciparum malaria infection. 1155 75

The protective effect of co-administration of recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and synthetic peptide met-enkephalin (M-ENK) against blood-induced Plasmodium berghei infection in Swiss mice was investigated. Mice co-administered with rmGM-CSF (10.0 mug/kg) and M-ENK (2.0 mg/kg) x 3/day, i.p., beginning on day -1 and continuing through day +4 after the initiation of infection, showed significant suppression (p < 0.05) (sometimes even complete elimination) of parasitaemia compared to vehicle-treated controls. However, when administered separately, neither of these agents induced any detectable protective effect. Surprisingly, mice similarly co-administered with rmGM-CSF (10.0 mug/kg) and higher doses of M-ENK (10.0 mg/kg), showed no protection. Polyclonal neutralizing (100%) antibody to rmGM-CSF abrogated the combined protective effect of these agents. Additionally, naloxone (10.0 mg/kg/day x 6, i.p.), a non-selective, opioid receptor antagonist, also blocked the combined protection. Mice that survived the challenge showed a significant increase (p < 0.05) in total circulating leukocytes counts, and the pool-size and the phagocytic activity of both the peritoneal and splenic macrophages, ex vivo. Silica (3.0 mg/mouse, i.v.) abrogated the combined protective effect of rmGM-CSF and M-ENK. These results indicate that co-administration of rmGM-CSF and dose dependent quantities of M-ENK in P. berghei-infected mice can protect against malaria, apparently through macrophage-mediated mechanisms.
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PMID:Protection of mice from malaria after co-administration of recombinant mouse granulocyte-macrophage colony- stimulating factor and methionine-enkephalin. 1156 34

This study was done in the Paediatric in-patient department of Chittagong Medical College Hospital (CMCH), Chittagong, Bangladesh to identify and quantify the prognostic factors associated with increased mortality in severe malaria (SM) cases. All the patients with parasitologically confirmed clinical syndromes of SM, admitted between June 1997 and May 1998, were included. A total of 53 consecutive cases were studied. Cerebral malaria (CM) was the commonest type of SM, observed in 36(68%) cases, second commonest type was severe anaemia 13(25%). More than one type of severe manifestations were present in 23(44%) cases. Overall case fatality rate (CFR) was 17% and it was 30% among those who had multi-organ manifestations. Important poor prognostic clinical variables were Blantrye coma score (BCS) score of 0 and 1 on day 1 (OR = 7.78) and day 2(OR = 40.0), multi-organ manifestations (OR = 6.8) and in-hospital complications (OR = 5.18). Important poor prognostic laboratory variables were day 2 parasite count > 50,000/cmm (OR = 5.5), blood glucose < 2.2 mmol/l (OR = 21.5) and raised CSF protein > 50 mg/dl (OR = 7.0). It can be concluded that certain clinical variables e.g. low BCS on day 1 & 2, multi-organ manifestations, in-hospital complications; and laboratory variables e.g. high parasite count, low blood glucose level, raised CSF protein levels are associated with increased mortality rate in SM cases.
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PMID:Prognostic factors relating to outcome of severe malaria among children in Bangladesh. 1169 95

To develop a multi-stage, multi-antigen, multi-immune response-inducing vaccine against malaria we have focused on DNA vaccines because of their simplicity of construction and modification, ease of mixing, and effectiveness in inducing CD8+ T cell responses. DNA malaria vaccines induce CD8+ T cell dependent protection in mice and CD8+ CTL in rhesus monkeys and humans after intramuscular needle administration. Clinical trials in normal, healthy humans are in progress or planned, assessing alternative methods and routes of administration, and the capacity of a plasmid expressing human GM-CSF to enhance the protective efficacy of a five-gene liver-stage malaria vaccine. In mice, we have demonstrated that priming with the combination of DNA plasmids encoding a Plasmodium yoelii protein and murine GM-CSF and boosting with recombinant poxvirus expressing the same P. yoelii protein induces a 30-fold increase in antigen-specific antibodies, a 10-fold increase in antigen-specific IFN-gamma spot forming cells, a significant (p<0.05) increase in protection, and the capacity to reduce the dosage of DNA by 10-100 fold, compared to immunizing with DNA alone. In Aotus monkeys priming with DNA and boosting with recombinant protein in adjuvant is more protective than homologous priming and boosting with either DNA or recombinant protein in adjuvant. Clinical trials are now planned using these immunization strategies. Because of the complexity and cost of the heterologous regimens, we are working to make DNA vaccination alone as immunogenic and protective as the prime-boost approach. Our most encouraging findings have resulted from altering codon usage from the highly A+T rich P. falciparum native sequence to that more closely resembling mammalian sequences. Although much progress is required for the development of a vaccine that provides sustainable protective immunity against malaria, a strategy using DNA vaccine technology as a core component of such a vaccine is promising.
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PMID:Can malaria DNA vaccines on their own be as immunogenic and protective as prime-boost approaches to immunization? 1171 10

All patients admitted with provisional diagnosis of an encephalitic illness over a period of 30 months, were studied. Special investigations included CSF analysis, EEG, CT scan and MRI. Herpes simplex virus (HSV) antibody estimation in CSF and blood was done simultaneously using ELISA. Patients with diagnosis of cerebral venous thrombosis, cerebral malaria, tubercular meningitis etc, who resembled herpes simplex encephalitis (HSE), were excluded systematically with relevant investigations. 28 patients showed electroencephalographic, serologic and/or neuroradiological evidence of herpes simplex encephalitis. Males were affected more than females. Age ranged from 4 years to 65 years. Main clinical features included altered sensorium (100%) and seizures (89%). Serological test for HSV antibody in CSF and blood was positive in 14 patients. Fronto-temporal localisation was seen in EEG of 18 patients. CT and MRI were fairly characteristic with bilateral asymmetric fronto-temporal lesions. Patients with mild disease and who reported earlier responded well to treatment with acyclovir. Mortality was higher if treatment was delayed or if the disease was severe. Delayed treatment even in less severe cases produced neurological deficit in many survivors. Despite limitations of non-availability of CSF-PCR and serial estimation of HSV antibodies, the study is an attempt to highlight the value of high index of suspicion of HSE on clinical grounds, systematically excluding cases with different aetiologies resembling HSE and planning early antiviral therapy to reduce both mortality and morbidity associated with this fatal disease.
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PMID:Herpes simplex encephalitis in North West India. 1179 8


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