Browsing by Author "Adabayeri, V."
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Item Acute P. falciparum malaria induces a loss of CD28- T IFN-γ producing cells(Parasite Immunology, 2002-11) Kemp, K.; Akanmori, B.D.; Kurtzhals, J.A.L.; Adabayeri, V.; Goka, B.Q.; Hviid, L.P. falciparum malaria is associated with increased activation among peripheral lymphocytes. In the present study, we investigated markers of susceptibility to apoptosis and expression of IFN-γ and IL-4 by CD28- and CD28+ T cells in West African children with acute P. falciparum malaria. The study showed increased susceptibility to apoptosis and cytokine production among T lymphocytes during acute malaria but also that T cells, in particular IFN-γ producing CD28- T cells, were substantially reduced. These results are in line with previous studies suggesting that certain T cell subsets are sequestered away from the peripheral blood during P. falciparum malaria.Item Allelic polymorphisms in the repeat and promoter regions of the interleukin-4 gene and malaria severity in Ghanaian children(Clinical and Experimental Immunology, 2004-10) Gyan, B.A.; Goka, B.; Cvetkovic, J.T.; Kurtzhals, J.L.; Adabayeri, V.; Perlmann, H.; Lefvert, A.-K.; Akanmori, B.D.; Troye-Blomberg, M.Immunoglobulin E has been associated with severe malaria suggesting a regulatory role for interleukin (IL)-4 and/or IgE in the pathogenesis of severe malaria. We have investigated possible associations between polymorphisms in the IL-4 repeat region (intron 3) and promoter regions (IL-4 +33CT and -590CT) in Ghanaian children with severe malaria. There was a significantly higher frequency of IL-4 intron-3 B1B1 genotype in the cerebral malaria group [P < 0-0001, odds ratio (OR) = 8-7]. The genotype and allele frequencies of the IL-4 -590 and +33 polymorphisms did not differ between the four study groups. Carriers of IL-4 +33T/-590T with cerebral malaria had elevated total IgE compared to non-carriers (P = 0.03). Our data suggest that IL-4 and/or IgE play a regulatory role in the pathogenesis of severe or complicated malaria.Item Comparison of chloroquine with artesunate in the treatment of cerebral malaria in Ghanaian children(Journal of Tropical Pediatrics, 2001-06) Goka, B.Q.; Adabayeri, V.; Ofori-Adjei, E.; Quarshie, B.; Asare-Odei, G.; Akanmori, B.D.; Kurtzhals, J.; Ofori-Adjei, D.; Neequaye, J.Despite previously reported chloroquine-resistant forms of P. falciparum in Ghana, chloroquine remains the drug of choice in severe malaria. Artemisinin derivatives have been shown to be effective against chloroquine-resistant strains in other endemic areas. This open randomized study was conducted to compare the efficacy of chloroquine and artesunate in the treatment of childhood cerebral malaria. Out of 82 subjects that fulfilled the inclusion criteria, 36 were randomized to receive chloroquine and 46 to receive artemisinin. Blantyre coma scores, temperature and parasitaemia were monitored. Mortality and neurological deficits were documented. There was no difference in mortality rates (chloroquine, 16.7 per cent; artesunate, 21.7 per cent; p = 0.6), neurological deficit at day 14 (chloroquine, 0 per cent; artesunate, 4.3 per cent; p = 0.3), resolution of fever (p = 0.55), and coma recovery time (p = 0.8), between the two groups. The results suggest that syrup chloroquine and intramuscular/oral artesunate currently give comparable clinical responses in the treatment of cerebral malaria in Ghana. Possible reasons for this are discussed, and suggestions are made for future antimalarial drug policy.Item The cytokine balance in severe malarial anemia [5] (multiple letters).(Journal of Infectious Diseases, 1999) Kurtzhals, J.A.L.; Akanmori, B.D.; Quarm Goka, B.; Adabayeri, V.; Nkrumah, F.K.; Behr, C.; Hviid, L.; Othoro, C.; Udhayakumar, V.Item Cytokine production and apoptosis among T cells from patients under treatment for Plasmodium falciparum malaria(Clinical and Experimental Immunology, 2002-01) Kemp, K.; Akanmori, B.D.; Adabayeri, V.; Goka, B.Q.; Kurtzhals, J.A.L.; Behr, C.; Hviid, L.Available evidence suggests that Plasmodium falciparum malaria causes activation and reallocation of T cells, and that these in vivo primed cells re-emerge into the periphery following drug therapy. Here we have examined the cytokine production capacity and susceptibility to programmed cell death of peripheral T cells during and after the period of antimalarial treatment. A high proportion of peripheral CD3+ cells had an activated phenotype at and shortly after time of admission (day 0) and initiation of therapy. This activation peaked around day 2, and at this time-point peripheral T cells from the patients could be induced to produce cytokines at conditions of limited cytokine response in cells from healthy control donors. Activated CD8hi and TCR-γδ+ cells were the primary IFN-γ producers, whereas CD4+ cells constituted an important source of TNF-α. The proportion of apoptotic T cells was elevated at admission and peaked 2 days later, while susceptibility to activation-induced cell death in vitro remained increased for at least 1 week after admission. Taken together, the data are consistent with the concept of malaria-induced reallocation of activated T cells to sites of inflammation, followed by their release back into the peripheral blood where they undergo apoptotic death to re-establish immunological homeostasis as inflammation subsides. However, the high proportion of pre-apoptotic cells from the time of admission suggests that apoptosis also contributes to the low frequency and number of T cells in the peripheral circulation during active disease.Item Distinct patterns of cytokine regulation in discrete clinical forms of plasmodium falciparum malaria.(European Cytokine Network, 2000) Akanmori, B.D.; Kurtzhals, J.A.L.; Goka, B.Q.; Adabayeri, V.; Ofori, M.F.; Nkrumah, F.K.; Behr, C.; Hviid, L.The pathogenesis of two of the most severe complications of Plasmodium falciparum malaria, cerebral malaria (CM) and severe malarial anaemia (SA) both appear to involve dysregulation of the immune system. We have measured plasma levels of TNF and its two receptors in Ghanaian children with strictly defined cerebral malaria (CM), severe malarial anaemia (SA), or uncomplicated malaria (UM) in two independent studies in an area of seasonal, hyperendemic transmission of P. falciparum. Levels of TNF, soluble TNF receptor 1 (sTNF-R1) and 2 (sTNF-R2) were found to be significantly higher in CM than in the other clinical categories of P. falciparum malaria patients. Levels of both receptors depended on clinical category, whereas only sTNF-R1 levels were significantly dependent on parasitemia. Detailed analysis of the interrelationship between these variables resolved this pattern further, and identified marked differences between the patient categories. While levels of TNF, sTNF-R1 and sTNF-R2 correlated with parasitemia in UM, this was not the case in CM and SA. Rather, there was a tendency towards high levels of TNF and its receptors in CM and low levels in SA without significant correlation to parasitemia in either category. This, and the fact that malaria-induced increases in plasma levels of IL-10 are much lower in SA compared to CM, suggest that distinct forms of dysregulation of the immune response to infection contribute to the pathogenesis of CM and SA.Item Haptoglobin 1-1 is associated with susceptibility to severe Plasmodium falciparum malaria(Transactions of the Royal Society of Tropical Medicine and Hygiene, 2000-03) Quaye, I.K.E.; Ekuban, F.A.; Goka, B.Q.; Adabayeri, V.; Kurtzhals, J.A.L.; Gyan, B.; Ankrah, N.-A.; Hviid, L.; Akanmori, B.D.The haptoglobin (Hp) phenotypes were determined by polyacrylamide-gel electrophoresis in plasma samples obtained in 1997 from 113 Plasmodium falciparum malaria patients (aged 1-12 years) with strictly defined cerebral malaria, severe malarial anaemia, or uncomplicated malaria and 42 age-matched healthy controls from the same area (coastal Ghana). Hp1-1 was significantly more prevalent among the patients (43%) than among healthy controls (7.1%), whereas Hp2-1 and Hp2-2 were underrepresented among the patients (11% and 2%, respectively) compared to the control donors (33% and 14%, respectively). No significant difference in frequency of Hp0 was observed between patients and controls. Among the malaria patients, the Hp1-1 phenotype was significantly more prevalent among patients with the complications of cerebral malaria and severe anaemia compared to patients with uncomplicated disease, whereas the reverse was seen with respect to Hp2-1 and Hp2-2. Our data suggest that the Hp1-1 phenotype is associated with susceptibility to P. falciparum malaria in general, and to the development of severe disease in particular.Item Low plasma concentrations of interleukin-10 in severe malarial anaemia compared with cerebral and uncomplicated malaria.(Lancet, 1998) Kurtzhals, J.A.L.; Adabayeri, V.; Goka, B.Q.; Akanmori, B.D.; Oliver-Commey, J.O.; Nkrumah, F.K.; Behr, C.; Hviid, L.Background Severe anaemia is a major complication of malaria but little is known about its pathogenesis. Experimental models have implicated tumour necrosis factor (TNF) in induction of bone-marow suppression and eythrophagocytosis. Conversely, interleukin 10 (IL-10), which mediates feed-back regulation of TNF, stimulates bone-marrow function in vitro and counteracts anaemia in mice. We investigated the associations of these cytokines with malarial anaemia. Methods We enrolled 175 African children with malaria into two studies in 1995 and 1996. In the first study, children were classified as having severe anaemia (n=10), uncomplicated malaria (n=26), or cerebral anaemia (n=41). In the second study, patients were classified as having cerebral malaria (n=33) or being fully conscious (n=65), and the two groups were subdivided by measured haemoglobin as normal (>110 g/L), moderate anaemia (60–90 g/L), and severe anaemia (>50 g/L). IL-10 and TNF concentrations were measured by ELISA in plasma samples from all patients. Findings IL-10 concentrations were significantly lower in patients with severe anaemia than in all other groups. In 1995, geometric mean plasma IL-10 in patients with severe anaemia was 270 pg/mL (95% CI 152–482) compared with 725 pg/mL (465–1129) in uncomplicated malaria and 966 pg/mL (612–1526) in cerebral malaria (p<0·03). In 1996, fully conscious patients with severe anaemia also had significantly lower IL-10 concentrations than all other groups, including cerebral-malaria patients with severe anaemia and all patients with moderate anaemia (p<0·001). In both studies, TNF concentrations were significantly higher in cerebral malaria than in fully conscious patients (p<0·01). By contrast, the ratio of TNF to IL-10 was significantly higher in fully conscious patients with severe anaemia than in all other groups (p<0·001). Interpretation Our findings identify severe malarial anaemia as a distinct disorder in which insufficient IL-10 response to high TNF concentrations may have a central role.