Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 associations of hemoglobin, hematocrit, and packed cell volume with socioeconomic factors, malaria, human immunodeficiency virus (HIV) infection, and nutritional status were examined among 687 children admitted to hospital with pneumonia participating in a double blind, placebo-controlled trial of vitamin A supplementation. Children were randomized to receive 2 doses of vitamin A (200,000 IU) or placebo at baseline, and additional doses at 4 and 8 months after discharge from hospital. Hemoglobin levels were measured at enrollment and, on a subset of 161 children, during follow-up. At baseline, hemoglobin concentration was positively associated with the number of possessions in the household, maternal level of education and quality of water supply, and inversely related to malaria infection after controlling for potential confounding variables. Children infected with HIV experienced a significant fall in mean hemoglobin levels over time. The risk of developing severe anemia (< 7 g/dL) during follow-up was lower for children who were breastfed for longer than 18 months as compared to those with less than 6 months of breastfeeding (adjusted prevalence ratio = 0.14, 95% confidence interval [CI] = 0.02, 0.93; P = 0.04), and higher for children over two years of age as compared to 6 to 11 months-old infants (adjusted prevalence ratio = 8.11, 95% CI = 1.2, 55.8; P = 0.03). Children with repeated diagnoses of malaria had 4.1 times the risk of developing severe anemia than did children without the diagnosis (95% CI = 1.3, 13.5; P = 0.02). Vitamin A supplements were associated with an overall nonsignificant reduction of 14% in the risk of developing severe anemia (adjusted prevalence ratio = 0.86, 95% CI = 0.37, 1.99; P = 0.73). We conclude that malaria, HIV infection, low socioeconomic status, and short duration of breastfeeding are strong and independent determinants of adverse hematologic profiles in this population.
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PMID:Vitamin A supplementation and other predictors of anemia among children from Dar Es Salaam, Tanzania. 1128 70

Between 1978 and 1988 Plasmodium falciparum resistance to chloroquine has been reported in all countries of tropical Africa. Despite the intensification of resistance during the last 2 decades, chloroquine remains in 2000 the first-line treatment for malaria in most of these countries. Here we review published data on the public health impact of antimalarial drug resistance in Africa. These data show that since the late 1980s convincing evidence of a major public health impact of the spread of chloroquine resistance has been available. Hospital studies in various African countries have documented a 2- or 3-fold increase in malaria deaths and admissions for severe malaria, an increase temporally related to the emergence of chloroquine resistance. Data from sentinel demographic surveillance systems in Senegal indicated that mortality attributable to malaria in children increased by as much as 6-fold among populations where low levels of malaria mortality had been achieved because of efficient health services before the emergence of chloroquine resistance. Increasing incidence of severe malarial anemia also contributed to human immunodeficiency virus dissemination. The dramatic impact of chloroquine resistance on malaria mortality has long been underestimated because only a low proportion of malaria attacks are potentially lethal among persons continuously exposed since birth to high levels of transmission. There is an urgent need to change treatment policies in Africa.
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PMID:The public health impact of chloroquine resistance in Africa. 1142 73

Pregnant women in malarious areas may experience a variety of adverse consequences from malaria infection including maternal anemia, placental accumulation of parasites, low birth weight (LBW) from prematurity and intrauterine growth retardation (IUGR), fetal parasite exposure and congenital infection, and infant mortality (IM) linked to preterm-LBW and IUGR-LBW. We reviewed studies between 1985 and 2000 and summarized the malaria population attributable risk (PAR) that accounts for both the prevalence of the risk factors in the population and the magnitude of the associated risk for anemia, LBW, and IM. Consequences from anemia and human immunodeficiency virus infection in these studies were also considered. Population attributable risks were substantial: malaria was associated with anemia (PAR range = 3-15%), LBW (8-14%), preterm-LBW (8-36%), IUGR-LBW (13-70%), and IM (3-8%). Human immunodeficiency virus was associated with anemia (PAR range = 12-14%), LBW (11-38%), and direct transmission in 20-40% of newborns, with direct mortality consequences. Maternal anemia was associated with LBW (PAR range = 7-18%), and fetal anemia was associated with increased IM (PAR not available). We estimate that each year 75,000 to 200,000 infant deaths are associated with malaria infection in pregnancy. The failure to apply known effective antimalarial interventions through antenatal programs continues to contribute substantially to infant deaths globally.
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PMID:The burden of malaria in pregnancy in malaria-endemic areas. 1142 75

Prevention of placental malaria through administration of antimalarial medications to pregnant women in disease-endemic areas decreases the risk of delivery of low birth weight (LBW) infants. In areas of high Plasmodium falciparum transmission, two intermittent presumptive treatment doses of sulfadoxine-pyrimethamine (SP) during the second and third trimesters of pregnancy are effective in decreasing the prevalence of placental malaria in human immunodeficiency virus (HlV)-negative women, while HIV-positive women may require a monthly SP regimen to reduce their prevalence of placental parasitemia. A decision-analysis model was used to compare the cost-effectiveness of three different presumptive SP treatment regimens with febrile case management with SP in terms of incremental cost per case LBW prevented. Factors considered included HIV seroprevalence, placental malaria prevalence, LBW incidence, the cost of SP, medical care for LBW infants, and HIV testing. For a hypothetical cohort of 10,000 pregnant women, the monthly SP regimen would always be the most effective strategy for reducing LBW associated with malaria. The two-dose SP and monthly SP regimens would prevent 172 and 229 cases of LBW, respectively, compared with the case management approach. At HIV seroprevalence rates greater than 10%, the monthly SP regimen is the least expensive strategy. At HIV seroprevalence rates less than 10%, the two-dose SP regimen would be the less expensive option. When only antenatal clinic costs are considered, the two-dose and monthly SP strategies cost US $11 and $14, respectively, well within the range considered cost effective. Presumptive treatment regimens to prevent LBW associated with malaria and the subsequent increased risk of mortality during the first year of life are effective and cost effective strategies in areas with both elevated HIV prevalence and malaria transmission rates.
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PMID:Cost-effectiveness of sulfadoxine-pyrimethamine for the prevention of malaria-associated low birth weight. 1144 15

DNA vaccine involves the injection of plasmid DNA encoding an antigen under the control of an eukaryotic promoter, and results in cellular and humoral immune responses to the plasmid DNA-encoded antigen. The immune response induced by DNA vaccine usually has a T-helper-1(Th1) bias through a potent Th1-promoting adjuvant effect of immunostimulatory DNA sequences with CpG motifs present in plasmid DNA. It has been demonstrated that volunteers who were vaccinated with plasmid DNA encoding a malaria protein or a human immunodeficiency virus protein developed antigen-specific, human leukocyte antigen(HLA)-restricted, CD8+ cytotoxic T lymphocytes(CTLs) The demonstration in humans of the induction of CD8+ CTLs by DNA vaccines, including CTLs, provides a foundation for further clinical application of this potentially revolutionary vaccine technology.
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PMID:[DNA vaccine]. 1151 28

Cytokines function at the cellular, microenvironmental level, but human cytokine assessment is most commonly done at the macro level, by measuring serum cytokines. The relationships between serum and cellular cytokines, if there are any, are undefined. In a study of hospitalized patients in Malawi, we compared cytometrically assessed, cell-specific cytokine data to serum interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) levels in 16 children and 71 (IL-2, -4, -6, -10) or 159 (IL-8, IFN-gamma, and TNF-alpha) adults, using Wilcoxon rank sum tests and Pearson's (r(p)) and Spearman's (r(s)) rank correlations. For the entire study group, correlations between identical serum and cellular cytokines mainly involved IL-8 and IFN-gamma, were few, and were weakly positive (r < 0.40). Blood culture-positive persons had the most and strongest correlations, including those between serum IL-2 levels and the percentages of lymphocytes spontaneously making IL-2 (r(s) = +0.74), serum IL-8 levels and the percentages of lymphocytes spontaneously making IL-8 (r(p) = +0.66), and serum IL-10 levels and the percentages of CD8(+) T cells making TNF-alpha (r(p) = +0.89). Human immunodeficiency virus (HIV)-positive persons had the next largest number of correlations, including several serum IL-8 level correlations, correlation of serum IL-10 levels with the percentages of lymphocytes producing induced IL-10 (r(s) = +0.36), and correlation of serum IFN-gamma levels and the percentages of lymphocytes spontaneously making both IL-6 and IFN-gamma in the same cell (r(p) = +0.59). HIV-negative, malaria smear-positive, and pediatric patients had few significant correlations; for the second and third of these subgroups, serum IL-8 level was correlated with the percentage of CD8(-) T cells producing induced IL-8 (r(s) = +0.40 and r(s) = +0.56, respectively). Thus, the strength of associations between serum and cellular cytokines varied with the presence or absence of bloodstream infection, HIV status, and perhaps other factors we did not assess. These results strongly suggest that serum cytokines at best only weakly reflect peripheral blood cell cytokine production and balances.
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PMID:Comparison of serum and cell-specific cytokines in humans. 1168 46

To assess risk factors for anemia in late pregnancy, we studied healthy pregnant women with a singleton uncomplicated pregnancy of > or = 32 weeks attending the prenatal clinic in the Provincial Hospital in Kisumu, Kenya. Between June 1996 and December 1998, 4,608 pregnant women had a blood sample collected for hemoglobin (Hb) measurement, malaria smear, and testing for human immunodeficiency virus (HIV). The mean +/- standard deviation of Hb was 9.58 +/- 1.8 g/dL; 21% had malaria in their blood; and 25% of the women were HIV seropositive. Plasmodium falciparum parasitemia was more common among HIV-seropositive women in all gravidities compared with HIV-seronegative women (risk ratio, 1.71; 95% confidence interval, 1.53-1.92). In a multivariate analysis, for primi- and secundigravidae women, the factors malaria, belonging to the Luo tribe, and HIV seropositivity were significantly associated with any anemia (Hb < 11 g/dL), and HIV seropositivity and documented fever were associated with severe anemia (Hb < 7 g/dL). In women of higher gravidities, HIV seropositivity was the only statistically significant factor associated with any anemia or with severe anemia. Asymptomatic HIV seropositivity is an important risk factor to be considered in the differential diagnosis of maternal anemia, independent of P. falciparum parasitemia.
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PMID:Human immunodeficiency virus seropositivity and malaria as risk factors for third-trimester anemia in asymptomatic pregnant women in western Kenya. 1171 25

There are continuing concerns over the safety of the nation's and the world's blood supply. The allogeneic blood supply is tested for antibodies to HIV1/2, HTLVI/II, hepatitis B, hepatitis C (HCV) and syphilis. Testing is also performed for donor ALT (SGOT) levels, for the presence of hepatitis B surface antigen, human immunodeficiency virus (HIV) p24 antigen and, using nucleic acid amplification testing (NAT), for HIV and HCV nucleic acids. Still, there are concerns regarding other pathogenic agents. Dr. Roger Dodd addresses a series of pathogens that are already known to be transmissible by transfusion. These include malaria, Chagas' disease, babesiosis, bacteria and some viral agents. The need for new donor screening assays to protect the integrity and purity of the blood supply must be balanced against the loss of potential donors and the cost of developing and implementing these new screening assays. This issue will be highlighted. Dr. Edward Snyder reviews the status of research into development of systems for pathogen inactivation (PI) of blood and its components. A proactive technology wherein PI reagents such as psoralen, riboflavin, dimethylmethylene blue or inactine are added to blood collection bags could assure multiple log reduction of a variety of pathogens including viruses, bacteria, protozoa and fungi without the need to initially pre-screen the blood for a specific pathogen. Such a program could also cover new pathogens as they enter the blood supply. As a key issue relates to the toxicology of these agents, Dr. Snyder provides data on a novel carcinogenicity assay that uses a heterozygous p53 knock-out mouse model. The criteria likely to be needed for PI technology to be adopted by the transfusion community are summarized.
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PMID:Reducing the risk of blood transfusion. 1172 97

Since the rhesus is often used as a "gatekeeper" model for the evaluation of malaria and simian immunodeficiency virus (SIV)/HIV vaccines, the identification of strategies to enhance the activation of rhesus T cells would potentially aid in the generation of more potent vaccines directed against these infectious agents. Several molecules normally found on the surface of professional human APCs are capable of providing the second signals critical for T cell activation: B7-1 (CD80), ICAM-1 (CD54), and LFA-3 (CD58). With the exception of B7, T cell costimulatory molecules in the rhesus have not been identified. We have recently designed and characterized both recombinant vaccinia and recombinant avipox vectors containing the transgenes for a triad of human T cell costimulatory molecules (B7-1, ICAM-1, LFA-3; designated TRICOM). Here, we demonstrate the enhanced activation of rhesus T cells stimulated with rhesus APCs infected with TRICOM vectors in the presence of signal 1. Infection with TRICOM vectors led to significant improvement of APC capabilities in terms of reduction of the amount of signal 1 needed to activate naive T cells, and reduction in the amount of APCs required to activate T cells using a constant amount of signal 1. Antibody blocking studies demonstrated that each of the three costimulatory molecule transgenes contributed to the enhanced proliferation of T cells. TRICOM-enhanced T cell activation was shown to correspond to increases in type 1 cytokines and a reduced level of apoptosis. TRICOM-infected autologous B cells from rhesus immunized with either an SIV vaccine or a malaria vaccine stimulated significantly greater levels of IFN-gamma in response to specific peptide than stimulation with uninfected autologous B cells or B cells infected with wild-type vector. The ability to augment immune responses using poxvirus-based vaccines containing multiple costimulatory molecule transgenes can now be addressed in the rhesus macaque model.
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PMID:Enhanced activation of rhesus T cells by vectors encoding a triad of costimulatory molecules (B7-1, ICAM-1, LFA-3). 1173 38

Pregnant women are highly susceptible to malaria, and human immunodeficiency virus (HIV) infection increases this susceptibility. In our previous studies, placental malaria (PM), HIV infection, and HIV/PM coinfection were all associated with decreased interferon (IFN)-gamma production by maternal placental (intervillous) blood mononuclear cells (IVBMC). This study investigated whether in vitro production of the IFN-gamma regulatory cytokines interleukin (IL)-12 and IL-18 and the chemokine IFN-inducible protein (IP)-10 by IVBMC is altered in women who have been exposed to malaria and are infected with HIV. IL-12 production from IVBMC was significantly lower in HIV-positive women, regardless of PM status, in contrast to HIV-negative, PM-negative women. IL-18 and IP-10 production by IVBMC was reduced in HIV-positive, PM-negative women but elevated in HIV-positive, PM-positive women. These results reveal a substantial impairment of IL-12 production by IVBMC in HIV-positive women, implicating this cytokine as a potentially critical regulator of malaria antigen-specific IFN-gamma responses in HIV-infected and HIV/PM-coinfected women.
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PMID:Immunity to placental malaria. III. Impairment of interleukin(IL)-12, not IL-18, and interferon-inducible protein-10 responses in the placental intervillous blood of human immunodeficiency virus/malaria-coinfected women. 1175 93


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