Browsing by Author "Troye-Blomberg, M."
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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 Circulating Epstein-Barr virus in children living in malaria-endemic areas(Scandinavian Journal of Immunology, 2005-06) Rasti, N.; Falk, K.I.; Donati, D.; Gyan, B.A.; Goka, B.Q.; Troye-Blomberg, M.; Akanmori, B.D.; Kurtzhals, J.A.L.; Dodoo, D.; Consolini, R.; Linde, A.; Wahlgren, M.; Bejarano, M.T.Children living in malaria-endemic regions have high incidence of Burkitt's lymphoma (BL), the aetiology of which involves Plasmodium falciparum malaria and Epstein-Barr virus (EBV) infections. Acute malarial infection impairs the EBV-specific immune responses with the consequent increase in the number of EBV-carrying B cells in the circulation. To further understand the potential influence of malarial infection on the EBV persistence in children living in malaria-endemic areas, we studied the occurrence and quantified cell-free EBV-DNA in plasma from 73 Ghanaian children with and without acute malarial infection. Viral DNA was detected in 40% of the samples (47% in the malaria-infected and 34% in the nonmalaria group) but was absent in plasma from Ghanaian adults and healthy Italian children. These findings provide evidence that viral reactivation is common among children living in malaria-endemic areas, and may contribute to the increased risk for endemic BL. The data also suggest that the epidemiology of EBV infection and persistence varies in different areas of the world. © 2005 Blackwell Publishing Ltd.Item Haptoglobin phenotypes and malaria infection in pregnant women at delivery in western Cameroon(Acta Tropica, 2004-03) Minang, J.T.; Gyan, B.A.; Anchang, J.K.; Troye-Blomberg, M.; Perlmann, H.; Achidi, E.A.Plasmodium falciparum-infected erythrocytes have been reported to sequester in the placenta by adhering to chondroitin 4-sulfate during pregnancy. Earlier studies have highlighted higher susceptibility of primigravidae to P. falciparum compared to multigravidae living within the same endemic areas. The haptoglobin phenotype (Hp1-1) has been associated with susceptibility to severe P. falciparum malaria and the presence of Hp in human endometrium has been reported. The possible role of different Hp phenotypes in susceptibility to or protection from placental infection by P. falciparum in both primigravid and multigravid women at delivery in western Cameroon was investigated in this study. Only the three major haptoglobin phenotypes; Hp1-1, Hp2-1 and Hp2-2, were found in the study population with the Hp1-1 phenotype being the predominant (53%). There was no significant difference in the distribution of the three Hp phenotypes between the two gravidity groups. Women carrying the Hp1-1 phenotype had higher parasite prevalences in both peripheral blood (21.6% against 9.1%) and placentas (42% against 16.7%) when compared to those with the Hp2-2 phenotype. The difference in the parasite density between women carrying the Hp1-1 and Hp2-2 phenotypes was statistically significant for placental infection (P=0.001) but not for maternal peripheral blood infection. Placental parasitaemias without peripheral blood parasitaemias were detected in 42.6% of all the P. falciparum positive women while 27.7% of the women had peripheral blood parasitaemias in the absence of placental infection and 29.8% of the women had both placental and peripheral blood parasitaemias. A statistically significant difference was observed between the primigravidae and multigravidae in the parasite density in placental biopsies (P=0.02) but not for maternal peripheral blood parasitaemia. Our data suggest that the Hp1-1 phenotype may play a role in susceptibility to placental infection by P. falciparum during pregnancy. © 2003 Published by Elsevier B.V.Item Immunity against HIV/AIDS, Malaria, and Tuberculosis during Co-Infections with Neglected Infectious Diseases: Recommendations for the European Union Research Priorities(PLoS Neglected Tropical Diseases 2(6): e255, 2008) Boraschi, D.; Abebe, M.; Aseffa, A.; Chiodi, F.; Chisi, J.; Del Prete, G.; Doherty, T.M.; Elhassan, I.; Engers, H.; Gyan, B.; Harandi, A.M.; Kariuki, T.; Kironde, F.; Kouriba, B.; Langhorne, J.; Laskay, T.; Medaglini, D.; Olesen, O.; Onyebujoh, P.; Palma, C.; Sauerwein, R.; Sibanda, E.; Steinhoff, U.; Tagliabue, A.; Thiel, A.; Vahedi, M.; Troye-Blomberg, M.Infectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. For many years, the three most devastating diseases, HIV/AIDS, malaria, and tuberculosis (TB) have received most of the world's attention. However, in rural and impoverished urban areas, a number of infectious diseases remain neglected and cause massive suffering. It has been calculated that a group of 13 neglected infectious diseases affects over one billion people, corresponding to a sixth of the world's population. These diseases include infections with different types of worms and parasites, cholera, and sleeping sickness, and can cause significant mortality and severe disabilities in low-income countries. For most of these diseases, vaccines are not available, poorly effective, or too expensive. Moreover, these neglected diseases often occur in individuals who are also affected by HIV/AIDS, malaria, or TB, making the problem even more serious and indicating that co-infections are the rule rather than the exception in many geographical areas. To address the importance of combating co-infections, scientists from 14 different countries in Africa and Europe met in Addis Ababa, Ethiopia, on September 9-11, 2007. The message coming from these scientists is that the only possibility for winning the fight against infections in low-income countries is by studying, in the most global way possible, the complex interaction between different infections and conditions of malnourishment. The new scientific and technical tools of the post-genomic era can allow us to reach this goal. However, a concomitant effort in improving education and social conditions will be needed to make the scientific findings effective.Item Levels of soluble CD163 and severity of malaria in children in Ghana(Clinical Vaccine Immunology 15(9):1456-60, 2008) Kusi, K.A.; Gyan, B.A.; Goka, B.Q.; Dodoo, D.; Obeng-Adjei, G.; Troye-Blomberg, M.; Akanmori, B.D.; Adjimani, J.P.CD163 is an acute-phase-regulated monocyte/macrophage membrane receptor expressed late in inflammation. It is involved in the haptoglobin-mediated removal of free hemoglobin from plasma, has been identified as a naturally soluble plasma glycoprotein with potential anti-inflammatory properties, and is possibly linked to an individual's haptoglobin phenotype. High levels of soluble CD163 (sCD163) in a malaria episode may therefore downregulate inflammation and curb disease severity. In order to verify this, the relationships between sCD163 levels, malaria severity, and selected inflammatory mediators (tumor necrosis factor alpha [TNF-alpha], interleukin-6 [IL-6], and IL-10) were assessed by enzyme-linked immunosorbent assay using plasma samples obtained from pediatric malaria patients with uncomplicated malaria (UM [n = 38]), cerebral malaria (CM [n = 52]), and severe malarial anemia (SA [n = 55]) during two consecutive malaria transmission seasons (2002 and 2003). Median sCD163 levels were higher in UM (11.9 microg/ml) patients than in SA (7.7 microg/ml; P = 0.010) and CM (8.0 microg/ml; P = 0.031) patients. Levels of sCD163 were also higher in all patient groups than in a group of 81 age-matched healthy controls. The higher sCD163/TNF-alpha ratio in UM patients, coupled with the fact that sCD163 levels correlated with TNF-alpha levels in UM patients but not in CM and SA patients, suggests inflammatory dysregulation in the complicated cases. The study showed that sCD163 levels are elevated during acute malaria. High sCD163 levels in UM patients may be due to the induction of higher-level anti-inflammatory responses, enabling them to avoid disease complications. It is also possible that UM patients simply lost their CD163 receptors from macrophages in inflammatory sites while complicated-malaria patients still had their receptors attached to activated macrophages, reflecting ongoing and higher-level inflammation associated with complicated malaria.Item Levels of Soluble CD163 and Severity of Malaria in Children in Ghana(Clin. Vaccine Immunol 15(9): 1456–1460, 2008) Kusi, K. A; Gyan, B.A; Goka, B.Q; Dodoo, D.; Obeng-Adjei, G.; Troye-Blomberg, M.; Akanmori, B.D.; Adjimani, J.P.CD163 is an acute-phase-regulated monocyte/macrophage membrane receptor expressed late in inflammation. It is involved in the haptoglobin-mediated removal of free hemoglobin from plasma, has been identified as a naturally soluble plasma glycoprotein with potential anti-inflammatory properties, and is possibly linked to an individual's haptoglobin phenotype. High levels of soluble CD163 (sCD163) in a malaria episode may therefore downregulate inflammation and curb disease severity. In order to verify this, the relationships between sCD163 levels, malaria severity, and selected inflammatory mediators (tumor necrosis factor alpha [TNF-alpha], interleukin-6 [IL-6], and IL-10) were assessed by enzyme-linked immunosorbent assay using plasma samples obtained from pediatric malaria patients with uncomplicated malaria (UM [n = 38]), cerebral malaria (CM [n = 52]), and severe malarial anemia (SA [n = 55]) during two consecutive malaria transmission seasons (2002 and 2003). Median sCD163 levels were higher in UM (11.9 microg/ml) patients than in SA (7.7 microg/ml; P = 0.010) and CM (8.0 microg/ml; P = 0.031) patients. Levels of sCD163 were also higher in all patient groups than in a group of 81 age-matched healthy controls. The higher sCD163/TNF-alpha ratio in UM patients, coupled with the fact that sCD163 levels correlated with TNF-alpha levels in UM patients but not in CM and SA patients, suggests inflammatory dysregulation in the complicated cases. The study showed that sCD163 levels are elevated during acute malaria. High sCD163 levels in UM patients may be due to the induction of higher-level anti-inflammatory responses, enabling them to avoid disease complications. It is also possible that UM patients simply lost their CD163 receptors from macrophages in inflammatory sites while complicated-malaria patients still had their receptors attached to activated macrophages, reflecting ongoing and higher-level inflammation associated with complicated malaria.Item Polymorphisms in interleukin-1 β and interleukin-1 receptor antagonist genes and malaria in Ghanaian children(Scandinavian Journal of Immunology, 2002-12) Gyan, B.; Goka, B.; Cvetkovic, J.T.; Perlmann, H.; Lefvert, A.-K.; Akanmori, B.; Troye-Blomberg, M.We have investigated the possible associations between polymorphisms in two interleukin-1 (IL-1) genes and severity of Plasmodium falciparum malaria in Ghanaian children with cerebral malaria, severe anaemia or uncomplicated malaria and controls. There was no significant difference in genotype and allele frequencies in IL-1 β exon 5 or interleukin-1 receptor antagonist (IL-1ra) polymorphisms between the studied groups, suggesting that the two polymorphisms may not be involved in the pathogenesis of severe malaria. When parasitaemias in uncomplicated malaria patients were evaluated, a significantly higher level of parasitaemia was observed among carriers of IL-1 β A2 allele as compared with noncarriers of this allele (P = 0.01). The mean parasitaemia in an age-matched asymptomatic group did not reveal such associations. These data suggest that IL-1 β exon 5 allele 2 may play a possible role in the clinical outcome of uncomplicated malaria.Item 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.