Douglas J Perkins

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We compared interleukin-12 (IL-12) and other cytokine activities during and after an acute clinical episode in a matched-pair case-control study of young African children who presented with either mild or severe Plasmodium falciparum malaria. The acute-phase, pretreatment plasma IL-12 and alpha interferon (IFN-alpha) levels, as well as the acute-phase(More)
Interleukin (IL)-12 and transforming growth factor (TGF)-beta1 regulate the balance between pro- and anti-inflammatory cytokines in animal models of malaria. Since the cytokine balance may be an important determinant of whether a protective or a pathogenic immune response develops, plasma cytokine ratios were examined in Gabonese children with various(More)
A point mutation in the promoter of the nitric oxide synthase 2 gene (NOS2), termed NOS2(Lambaréné) (NOS2-G954C), protects heterozygous carriers against severe malaria as effectively as the sickle cell trait. In a prospective longitudinal study, 841 individual infections of initially 200 children (151 wild-type vs. 49 NOS2(Lambaréné) carriers) were(More)
Greater than 80% of malaria-related mortality occurs in sub-Saharan Africa due to infections with Plasmodium falciparum. The majority of P. falciparum-related mortality occurs in immune-naïve infants and young children, accounting for 18% of all deaths before five years of age. Clinical manifestations of severe falciparum malaria vary according to(More)
Plasmodium falciparum malaria is one of the leading global causes of morbidity and mortality with African children bearing the highest disease burden. Among the various severe disease sequelae common to falciparum malaria, severe malarial anemia (SMA) in pediatric populations accounts for the greatest degree of mortality. Although the patho-physiological(More)
The optimal outcome of a malaria infection is that parasitized cells are killed and degraded without inducing significant pathology. Since much of the pathology of malaria infection can be immune-mediated, this implies that immune responses have to be carefully regulated. The mechanisms by which anti-malarial immune responses are believed to be regulated(More)
Since the etiologies and clinical outcomes of bacteremia in children with Plasmodium falciparum infections, particularly in areas of holoendemic malaria transmission, are largely unexplored, blood cultures and comprehensive clinical, laboratory, hematological, and nutritional parameters for malaria-infected children (aged 1 to 36 months, n = 585 patients)(More)
Nitric oxide (NO) plays an important role in host resistance to infection with a variety of organisms. Two recent reports from Gabon and Gambia identified associations of malaria disease severity with the inducible NO synthase (NOS2) promoter G-954C and short allele (<11 repeats) pentanucleotide microsatellite polymorphisms, respectively. It was postulated(More)
Areas where Plasmodium falciparum transmission is holoendemic are characterized by high rates of pediatric severe malarial anemia (SMA) and associated mortality. Although the etiology of SMA is complex and multifactorial, perturbations in inflammatory mediator production play an important role in the pathogenic process. As such, the current study focused on(More)
Experiments outlined here investigate the role of nitric oxide (NO) in the pathogenesis of Plasmodium falciparum-induced malarial anemia (MA). The results show that ex vivo and in vitro NO synthase (NOS) activity in peripheral blood mononuclear cells (PBMCs) is significantly elevated in children with MA and inversely associated with hemoglobin levels.(More)