Research Articles

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A research article reports the results of original research, assesses its contribution to the body of knowledge in a given area, and is published in a peer-reviewed scholarly journal. The faculty publications through published and on-going articles/researches are captured in this community

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    Human leukocyte antigen class I polymorphisms influence the mild clinical manifestation of Plasmodium falciparum infection in Ghanaian children
    (Human Immunology, 2011-10) Yamazaki, A.; Yasunami, M.; Ofori, M.; Horie, H.; Kikuchi, M.; Helegbe, G.; Takaki, A.; Ishii, K.; Omar, A.H.; Akanmori, B.D.; Hirayama, K.
    A prospective study that included 429 children for active detection of mild malaria was conducted in a coastal region of Ghana to reveal whether the incidence of malaria is affected by human leukocyte antigen (HLA) polymorphism. During 12 months of follow-up, 85 episodes of mild clinical malaria in 74 individuals were observed, and 34 episodes among them were accompanied with significant parasitemia at >5000 infected red blood cells per cubic millimeter. Attributable and relative risks conferred by genetic factors in the HLA region were evaluated by comparison of the incidence in children, stratified by carrier status, of a given allele of HLA-A, -B, -DRB1 and TNFA promoter polymorphism. HLA-B*35:01 reduced the incidence by 0.178 events per person per year (0.060 versus 0.239 for B*35:01-positive and -negative subpopulations, respectively), and a relative risk of 0.25, which remained statistically significant after Bonferroni's correction for multiple testing (p c = 8.2 × 10 -5). Further, HLA-B*35:01 and -B*53:01 exhibited opposite effects on the incidence of malaria with significant parasitemia. When parasite densities in different HLA carriers status were compared, HLA-A*01 conferred an increase in parasite load (p = 6.0 × 10 -7). In addition, we found a novel DRB1 allele that appears to have emerged from DRB1*03:02 by single nucleotide substitution. © 2011 American Society for Histocompatibility and Immunogenetics.
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    A STAT6 intronic single-nucleotide polymorphism is associated with clinical malaria in Ghanaian children
    (Libertas Academica Ltd, 2016) Amoako-Sakyi, D.; Adukpo, S.; Kusi, K.A.; Dodoo, D.; Ofori, M.F.; Adjei, G.O.; Edoh, D.E.; Asmah, R.H.; Brown, C.; Adu, B.; Obiri-Yeboah, D.; Futagbi, G.; Abubakari, S.B.; Troye-Blomberg, M.; Akanmori, B.D.; Goka, B.Q.; Arko-Mensah, J.; Gyan, B.A.
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    Pretreatment blood concentrations of chloroquine in patients with malaria infection: Relation to response to treatment
    (Journal of Tropical Pediatrics, 2005-06) Quashie, N.B.; Akanmori, B.D.; Goka, B.Q.; Ofori-Adjei, D.; Kurtzhals, J.A.L.
    Resistance of Plasmodium falciparum to chloroquine has been reported in many areas in Ghana. Most of these reports, which are from hospital-based studies, indicate RI and RII rather than RIII type of resistance. Since high pretreatment levels of chloroquine have also been measured in patients with malaria infection in Ghana, we hypothesized that the 'added effect' of the pretreatment ingested drug to the full dose given at the hospital may be responsible for the low proportion of RIII type of resistance observed. To ascertain this, pretreatment blood levels of chloroquine were correlated with treatment outcomes in 231 paediatric malaria patients, referred to a major hospital in Ghana. The rate of parasite clearance and prevalence of recrudescence, 14 days post-treatment, were determined for each patient. Results from this study showed no correlation between pretreatment chloroquine levels and day 0 parasitaemia. Two hundred and seven patients (89.6 per cent) had parasites that were sensitive to chloroquine whilst 24 (10.4 per cent) had resistant parasites. Of the latter group 17, six, and one patients had P. falciparum parasites, which were resistant at RI, RII and RIII levels, respectively. Seventy-five per cent of the patients without any detectable pretreatment blood chloroquine had parasites that were sensitive to chloroquine whilst 89.8 per cent, 98 per cent, and 100 per cent with pretreatment blood chloroquine concentration ranges of 0.5-100.5/ml, 100.5-200/ml, and >200/ml, respectively, had chloroquine-sensitive parasites. An inverse relationship was thus observed between pretreatment blood chloroquine concentration and the degree of resistance in this study. We conclude that pre-hospital treatment ingested chloroquine contributes significantly to the resolution of malaria in children in Ghana, in the presence of chloroquine resistance. © The Author [2005]. Published by Oxford University Press. All rights reserved.
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    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.
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    Elevated levels of nitric oxide and low levels of haptoglobin are associated with severe malarial anaemia in African children
    (Acta Tropica, 2002-08) Gyan, B.; Kurtzhals, J.A.L.; Akanmori, B.D.; Ofori, M.; Goka, B.Q.; Hviid, L.; Behr, C.
    Severe malarial anaemia (SA) is a major complication of malaria and an important cause of child mortality and morbidity. However, the pathogenesis behind SA is poorly understood. Nitric oxide (NO) is known to play a protective role against clinical malaria but is also suggested to have a pathogenic role in cerebral malaria (CM). Erythrophagocytosis by splenic macrophages has been implicated in the pathogenesis of SA. In this study, plasma levels of NO, neopterin, haptoglobin and C-reactive protein (CRP) were measured in paediatric patients with CM, n=77, SA (n=28) and uncomplicated malaria (UM n=53). Haptoglobin levels were significantly lower in SA (median (interquartile range) 25 (17-59) mg/l) than in both CM and UM (40 (24-80) mg/l and 110 (60-160) mg/l, respectively, P<0.001). In contrast, NO levels were higher in SA (38 (28-51) μmol/l) than in CM and UM (21 (15-32) μmol/l and 10.3 (5.6-17) μmol/l, respectively, P<0.001). A significant negative correlation between haptoglobin and NO was seen in the SA group. No such correlation was observed within the UM or CM groups. No significant differences in neopterin levels were observed between any of the three groups, neither was there any correlation between parasitaemias and neopterin levels. The low haptoglobin and high levels of NO in this SA group may contribute to haemolysis. Taken together our results support the hypothesis that immune-mediated erythrocyte destruction is involved in the pathogenesis of malarial anaemia. © 2002 Elsevier Science B.V. All rights reserved.
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    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.
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    The importance of strict patient definitions in studies of malaria pathogenesis [1]
    (Trends in Parasitology, 2001-07) Kurtzhals, J.A.L.; Goka, B.Q.; Akanmori, B.D.; Hviid, L.
    Most clinical studies of malariapathogenesis in humans are performed ascross-sectional studies comparing differentpatient categories. We have looked atstudies of similar clinical manifestations ofmalaria and found wide variation in theirconclusions. The differences could presenttrue geographical variation caused eitherby transmission pattern or by host andparasite genetics, or both. Anotherimportant reason for the variation is,however, ill-defined patient groups thathave not been designed specifically toaddress the questions raised by the studies.The bulk of evidence suggests that thedifferent complications of malaria differ inpathogenesis, management and prognosis.Malarial anaemia and cerebral malariaaffect different age groups of childrenexposed to different levels of malariatransmission1and are associated withdifferent cytokine profiles2. In fact,probably both malarial anaemia andcerebral malaria should be furthersubdivided into distinct entities3,4(B.A. Astrup et al., unpublished). We thuspropose that severe malaria should not bestudied as one disease entity, and thatcareful and uniform case definitions arecrucial for studies of malaria pathogenesis.It is also problematic to use so-called ‘mild’malaria as controls.
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    Complement binding to erythrocytes is associated with macrophage activation and reduced haemoglobin in Plasmodium falciparum malaria
    (Transactions of the Royal Society of Tropical Medicine and Hygiene, 2001-09) Goka, B.Q.; Kwarko, H.; Kurtzhals, J.A.L.; Gyan, B.; Ofori-Adjei, E.; Ohene, S.A.; Hviid, L.; Akanmori, B.D.; Neequaye, J.
    We have examined IgG and complement factor C3d deposition on erythrocytes by means of the direct Coombs' test (DAT) and looked for an association with the anaemia seen in falciparum malaria in children living in an area of hyperendemic malaria transmission (in Ghana). In one study (in 1997), 53 out of 199 patients had a positive DAT. Of these, 45 samples reacted with anti-C3d antibodies, 2 with anti-IgG and 6 with both reagents. There were significantly lower haemoglobin (Hb)-levels and higher prevalence of spleen enlargement in DAT-positive than in DAT-negative patients. Hb-levels were independently associated with DAT and age. This initial study was designed to investigate the role of intravascular haemolysis (IVH), but we found no association between IVH and either DAT result or anaemia. Because of the risk of selection bias we repeated the study using consecutive enrolment of malaria patients and were able to confirm the results in a total of 49 DAT-positive and 183 DAT-negative patients. This second study (in 1998) was designed to look at the importance of erythrophagocytosis through measurement of plasma neopterin levels and total nitrite and nitrate as markers of NO-release. Both parameters were significantly higher in DAT-positive than in DAT-negative patients (P < 0.001), indicating that complement binding to erythrocytes was associated with macrophage activation. Plasma levels of haptoglobin, interleukin-10 and tumour necrosis factor-α did not vary between the groups. The studies support the role of complement activation and erythrophagocytosis in [-the pathogenesis of anaemia in falciparum malaria in African children.
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    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.
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    Increased eosinophil activity in acute plasmodium falciparum infection - association with cerebral malaria.
    (Clinical and Experimental Immunology, 1998) Kurtzhals, J.A.L.; Reimert, C.M.; Tette, E.; Dunyo, S.K.; Koram, K.A.; Akanmori, B.D.; Nkrumah, F.K.; Hviid, L.
    To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM (geometric mean (95% confidence interval) 8.5 ng/ml (6.8–10.7 ng/ml)) than in SA (4.7 ng/ml (3.0–7.5 ng/ml)) and UM patients (4.3 ng/ml (3.6–5.3 ng/ml), P < 0.001). A similar pattern was found for EPX. It thus appears that the low eosinophil counts may be due to tissue sequestration and destruction rather than decreased production. The plasma levels of the granule proteins correlated with levels of tumour necrosis factor and soluble IL-2 receptor, implicating inflammatory responses and T cell activation as causes of the eosinophil activation. By contrast, the eosinophil induction did not appear to be part of a Th2-like response. Eosinophil granule proteins may be important in both control of malaria infection and the pathogenesis of severe malaria.