Browsing by Author "Addae, M.M."
Now showing 1 - 17 of 17
Results Per Page
Sort Options
Item Anaemia caused by asymptomatic plasmodium falciparum infection in semi-immune african schoolchildren.(1999) Kurtzhals, J.A.L.; Addae, M.M.; Akanmori, B.D.; Dunyo, S.; Koram, K.A.; Appawu, M.A.; Nkrumah, F.K.; Hviid, L.A cohort of 250 Ghanaian schoolchildren aged 5-15 years was followed clinically and parasitologically for 4 months in 1997/98 in order to study the effect of asymptomatic Plasmodium falciparum infections on haematological indices and bone-marrow responses. Of the 250 children 65 met the predefined study criteria. Thus, 14 children were parasite-free throughout (group 1), 44 had P. falciparum in all blood samples collected but no symptoms of malaria (group 2), and 7 had 1 malaria attack during the study period (group 3). At the end of the study the mean haemoglobin (Hb) level in group 1 was 123 g/L, significantly higher than the value of 114 g/L in groups 2 and 3 (P < 0.02, adjusted for age and splenomegaly). The low Hb in group 2 was associated with subnormal plasma iron. Low Hb was associated with elevated erythropoietin (EPO) levels, and there was a positive correlation between EPO and reticulocyte counts. However, the reticulocyte response to EPO was more pronounced in uninfected than in infected children, suggesting a partial interference with erythropoiesis in asymptomatic infections. Children with asymptomatic infections had significantly higher plasma levels of tumour necrosis factor than uninfected children (geometric means 50 ng/L and 27 ng/L, respectively, P < 0.001) and this cytokine may contribute to bone-marrow suppression and disturbed iron metabolism. We suggest that asymptomatic malaria leads to a homeostatic imbalance in which erythrocyte loss due to parasite replication is only partially compensated for by increased erythropoiesis. The consequences of the reduced Hb levels on the development and cognitive abilities of children with asymptomatic infections, and the risk of precipitation of iron deficiency, deserve further study and should be considered in malaria control programmes that aim at reducing morbidity rather than transmission.Item Comparative effects of aflatoxins G1 and B1 at levels within human exposure limits on mouse liver and kidney.(1993) Ankrah, N.A.; Addo, P.G.; Ekuban, F.A.; Addae, M.M.ddy mice were exposed to aflatoxins B1 and G1 via their feed (4.8 ng AFG1, 0.8 ng AFB1 or both/kg body wt./day) while in utero. At six months of age, hepatorenal studies were carried out. The AFG1 caused significant accumulation of only neutral fat in the liver, a slight rise in serum triglyceride and intensified hepatorenal inflammation, necrosis and bile duct proliferation. The AFB1, caused the accumulation of both neutral fat and fatty acids in the liver, and was cytotoxic to the liver and kidney. Iron storage of the liver, hematological indices, serum total protein and albumin levels were not affected by the aflatoxins.Item Complement activation in Ghanaian children with severe Plasmodium falciparum malaria(Malaria Journal, 2007) Helegbe, G.K.; Goka, B.Q.; Kurtzhals, J.A.; Addae, M.M.; Ollaga, E.; Tetteh, J.K.; Dodoo, D.; Ofori, M.F.; Obeng-Adjei, G.; Hirayama, K.; Awandare, G.A.; Akanmori, B.D.Severe anaemia (SA), intravascular haemolysis (IVH) and respiratory distress (RD) are severe forms of Plasmodium falciparum malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism leading to excess anaemia in acute P. falciparum infection. METHODS: The direct Coombs test (DCT) and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3balphabeta) and the regulatory proteins [complement receptor 1 (CD35) and decay accelerating factor (CD55)] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb) levels and RD were investigated. RESULTS: Of the 484 samples tested, 131(27%) were positive in DCT, out of which 115/131 (87.8%) were positive for C3d alone while 16/131 (12.2%) were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2-6.7, p < 0.001). DCT correlated significantly with RD (beta = -304, p = 0.006), but multiple regression analysis revealed that, Hb (beta = -0.341, p = 0.012) and coma (beta = -0.256, p = 0.034) were stronger predictors of RD than DCT (beta = 0.228, p = 0.061). DCT was also not associated with IVH, p = 0.19, while spleen size was inversely correlated with Hb (r = -402, p = 0.001). Flow cytometry showed similar mean fluorescent intensity (MFI) values of CD35, CD55 and C3balphabeta levels on the surfaces of RBC in patients and asymptomatic controls (AC). However, binding of C3balphabeta correlated significantly with CD35 or CD55 (p < 0.001). CONCLUSION: These results suggest that complement activation contributed to anaemia in acute childhood P. falciparum malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement regulatory proteins, CD35 and CD55 and malarial anaemia. These findings suggest that complement activation could also be involved in the pathogenesis of RD but larger studies are needed to confirm this findingItem Complement activation in Ghanaian children with severe Plasmodium falciparum malaria(2007-12-17) Helegbe, G.K.; Goka, B.Q.; Kurtzhals, J.A.L.; Addae, M.M.; Ollaga, E.; Tetteh, J.K.A.; Dodoo, D.; Ofori, M.F.; Obeng-Adjei, G.; Hirayama, K.; Awandare, G.A; Akanmori, B.D.Abstract Background Severe anaemia (SA), intravascular haemolysis (IVH) and respiratory distress (RD) are severe forms of Plasmodium falciparum malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism leading to excess anaemia in acute P. falciparum infection. Methods The direct Coombs test (DCT) and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3bαβ) and the regulatory proteins [complement receptor 1 (CD35) and decay accelerating factor (CD55)] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb) levels and RD were investigated. Results Of the 484 samples tested, 131(27%) were positive in DCT, out of which 115/131 (87.8%) were positive for C3d alone while 16/131 (12.2%) were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2–6.7, p < 0.001). DCT correlated significantly with RD (β = -304, p = 0.006), but multiple regression analysis revealed that, Hb (β = -0.341, p = 0.012) and coma (β = -0.256, p = 0.034) were stronger predictors of RD than DCT (β = 0.228, p = 0.061). DCT was also not associated with IVH, p = 0.19, while spleen size was inversely correlated with Hb (r = -402, p = 0.001). Flow cytometry showed similar mean fluorescent intensity (MFI) values of CD35, CD55 and C3bαβ levels on the surfaces of RBC in patients and asymptomatic controls (AC). However, binding of C3bαβ correlated significantly with CD35 or CD55 (p < 0.001). Conclusion These results suggest that complement activation contributed to anaemia in acute childhood P. falciparum malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement regulatory proteins, CD35 and CD55 and malarial anaemia. These findings suggest that complement activation could also be involved in the pathogenesis of RD but larger studies are needed to confirm this finding.Item Complement activation in Ghanaian children with severe Plasmodium falciparum malaria(Malaria Journal, 2007) Helegbe, G.K.; Goka, B.Q.; Kurtzhals, J.A.; Addae, M.M.; Ollaga, E.; Tetteh, J.K.; Dodoo, D.; Ofori, M.F; Obeng-Adjei, G.; Hirayama, K.; Awandare, G.A.; Akanmori, B.D.Severe anaemia (SA), intravascular haemolysis (IVH) and respiratory distress (RD) are severe forms of Plasmodium falciparum malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism leading to excess anaemia in acute P. falciparum infection. METHODS: The direct Coombs test (DCT) and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3balphabeta) and the regulatory proteins [complement receptor 1 (CD35) and decay accelerating factor (CD55)] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb) levels and RD were investigated. RESULTS: Of the 484 samples tested, 131(27%) were positive in DCT, out of which 115/131 (87.8%) were positive for C3d alone while 16/131 (12.2%) were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2-6.7, p < 0.001). DCT correlated significantly with RD (beta = -304, p = 0.006), but multiple regression analysis revealed that, Hb (beta = -0.341, p = 0.012) and coma (beta = -0.256, p = 0.034) were stronger predictors of RD than DCT (beta = 0.228, p = 0.061). DCT was also not associated with IVH, p = 0.19, while spleen size was inversely correlated with Hb (r = -402, p = 0.001). Flow cytometry showed similar mean fluorescent intensity (MFI) values of CD35, CD55 and C3balphabeta levels on the surfaces of RBC in patients and asymptomatic controls (AC). However, binding of C3balphabeta correlated significantly with CD35 or CD55 (p < 0.001). CONCLUSION: These results suggest that complement activation contributed to anaemia in acute childhood P. falciparum malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement regulatory proteins, CD35 and CD55 and malarial anaemia. These findings suggest that complement activation could also be involved in the pathogenesis of RD but larger studies are needed to confirm this finding.Item Decreased cysteine and glutathione levels: Possible determinant of liver toxicity risk in Ghanaian subjects.(1994) Ankrah, N.A.; Rikimaru, T.; Ekuban, F.A.; Addae, M.M.Cysteine, methionine, vitamin A, beta-carotene and glutathione (GSH) are known to protect body tissues against oxidative damage and inflammation but their value as protection against liver inflammation in tropical areas has received little attention. Blood levels of these nutrients were measured in Ghanaian volunteers with (Group 2) or without (Group 1) increased lipid peroxidation and signs of liver inflammation, as indicated by blood malonic dialdehyde, serum alpha 1-antitrypsin and triglyceride levels, and the alpha 1-acid glycoprotein:pre-albumin ratio. Serum levels of cysteine and blood glutathione were significantly lower (P < 0.02) in group 2 than in group 1 volunteers. In contrast, serum levels of methionine, vitamin A and beta-carotene were similar in both groups. Deficits in cysteine and glutathione may increase the risk of liver toxicity from oxidants in Ghanaians.Item falciparum malaria in children at a tertiary teaching hospital: ABO blood group is a risk factor.(2011-09-06) Kuadzi, J.T.; Ankra-Badu, G.; Addae, M.M.BACKGROUND: ABO blood group antigens are formed by terminal glycosylation of glycoproteins and glycolipid chains present on cell surfaces. Glycosylation modulates all kinds of cell-to-cell interactions and this may be relevant in malaria pathophysiology, in which adhesion has been increasingly implicated in disease severity. This study was done to determine the association between ABO phenotypes and the severity of P. falciparum malaria in children. METHODS: One hundred and twenty one children were assessed at the Department of Child Health, KBTH from May to August 2008. ABO blood groups were determined by agglutination. The haemoglobin measurement was done with the haematology analyzer, Sysmex KX-21N. Malaria parasites were enumerated and the presence of malaria pigment noted. Identification of P. falciparum was done. Statistical tests used were odds ratio and chi square at a significance level of p<0.05. RESULTS: 24.3% of the 121 children had severe falciparum malaria, and their mean haemoglobin was 4.49 g/dl (SD ± 1.69). No significant association was found between the ABO phenotypes and malaria infection (p > 0.05). Blood group A was associated with more severe malaria as compared to the blood group O individuals (Odds ratio = 0.79, p > 0.05); blood group AB (Odds ratio = 0.14, p > 0.05) and also there was a significant difference in severity of malaria between blood group O and blood group B (Odds ratio = 1.28, p > 0.05). CONCLUSION: Non-O blood group children are more prone to severe malaria caused by P. falciparum malaria than the group O, despite the lack of significant association between ABO blood groups and falciparum malaria.Item High CD4/CD45RO+ and CD8/CD45RO+ frequencies in children with vaccine-modified measles(Pediatrics International, 2006) Addae, M.M.; Tetteh, J.K.A.; Ishiwada, N.; Komada, Y.; Yamaguchi, S.; Ofori-Adjei, D.; Kamiya, H.; Akanmori, B.D.BACKGROUND: Despite availability and wide vaccine coverage, measles infections still occur especially in developing countries. An outbreak of measles occurred among previously immunized older Ghanaian children who had milder clinical symptoms with measles-specific IgG antibodies that could have been attributed to secondary vaccine failure, suggesting that the infection was vaccine-modified measles (VMM). METHODS: Two-color immunophenotyping of the peripheral blood mononuclear cells was performed at acute, recovery and convalescence phases for 19 VMM patients (mean age 6.2 +/- 3.5 years) using flow cytometry, and compared with that of 20 healthy, sex- and age-matched controls. RESULTS: The results showed a significantly higher memory helper (CD4(+)/CD45RO(+)) cell frequency and increased suppressor cell (CD8(+)/CD45R0(+)) frequency in VMM patients compared to healthy controls. There were no complications and all the patients recovered completely. CONCLUSIONS: These findings show that the mild symptoms in patients with VMM may have correlated with the increase of memory T cells, which is in sharp contrast with previous reports on acute measles infection. This may suggest that the intact immunologic memory cells could have been crucial for the resolution of VMM.Item Immunological unresponsiveness and apoptotic cell death of T cells in measles virus infection(Acta Paediatrica Japonica, 1995) Addae, M.M.; Komada, Y.; Zhang, X.; Sakurai, M.The phenotypic alterations associated with T cells during measles virus infection have been demonstrated and an attempt has been made to show programmed cell death (PCD) of T cells activated in vivo. During the acute phase of illness, activated T cells increased rapidly. Memory T cells (CD45RO+), especially CD8+ memory T cells also tend to increase. During the recovery phase, CD8+ T cells declined rapidly, and naive (CD45RA+) T cells increased in numbers. The anti-CD3 monoclonal antibody-induced expression of interleukin-2 receptor (CD25) was suppressed. However, the addition of phorbol 12-myristate 13-acetate (PMA) caused the significant recovery of CD25 expression. In addition, PCD of activated T cells from measles patients was induced in culture. After triggering of the T cell receptor-CD3 complex, cells became more susceptible to PCD. Interestingly, the addition of PMA could inhibit PCD of activated T cells. Taken together, these data suggest unresponsiveness and activation-induced cell death of T cells during the primary response to measles virus antigens, depending on the activation status of protein kinase C.Item Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia(2012-08-01) Boeuf, Philippe S.; Loizon, S.; Awandare, G. A.; Tetteh, John K.A.; Addae, M.M.; Adjei, G.O.; Goka, B.; Kurtzhals, J.; Puijalon, O.; Hviid, L.; Akanmori, B.D.; Behr, C.Abstract Background Severe malarial anaemia (SMA) is a major life-threatening complication of paediatric malaria. Protracted production of pro-inflammatory cytokines promoting erythrophagocytosis and depressing erythropoiesis is thought to play an important role in SMA, which is characterized by a high TNF/IL-10 ratio. Whether this TNF/IL-10 imbalance results from an intrinsic incapacity of SMA patients to produce IL-10 or from an IL-10 unresponsiveness to infection is unknown. Monocytes and T cells are recognized as the main sources of TNF and IL-10 in vivo, but little is known about the activation status of those cells in SMA patients. Methods The IL-10 and TNF production capacity and the activation phenotype of monocytes and T cells were compared in samples collected from 332 Ghanaian children with non-overlapping SMA (n = 108), cerebral malaria (CM) (n = 144) or uncomplicated malaria (UM) (n = 80) syndromes. Activation status of monocytes and T cells was ascertained by measuring HLA-DR+ and/or CD69+ surface expression by flow cytometry. The TNF and IL-10 production was assessed in a whole-blood assay after or not stimulation with lipopolysaccharide (LPS) or phytohaemaglutinin (PHA) used as surrogate of unspecific monocyte and T cell stimulant. The number of circulating pigmented monocytes was also determined. Results Monocytes and T cells from SMA and CM patients showed similar activation profiles with a comparable decreased HLA-DR expression on monocytes and increased frequency of CD69+ and HLA-DR+ T cells. In contrast, the acute-phase IL-10 production was markedly decreased in SMA compared to CM (P = .003) and UM (P = .004). Although in SMA the IL-10 response to LPS-stimulation was larger in amplitude than in CM (P = .0082), the absolute levels of IL-10 reached were lower (P = .013). Both the amplitude and levels of TNF produced in response to LPS-stimulation were larger in SMA than CM (P = .019). In response to PHA-stimulation, absolute levels of IL-10 produced in SMA were lower than in CM (P = .005) contrasting with TNF levels, which were higher (P = .001). Conclusions These data reveal that SMA patients have the potential to mount efficient IL-10 responses and that the TNF/IL-10 imbalance may reflect a specific monocyte and T cell programming/polarization pattern in response to infection.Item Insights into deregulated TNF and IL-10 production in malaria: Implications for understanding severe malarial anaemia(Malaria Journal, 2012) Boeuf, P.S.; Loizon, S.; Awandare, G.A.; Tetteh, J.K.; Addae, M.M.; Adjei, G.O.; Behr, C.Abstract Background: Severe malarial anaemia (SMA) is a major life-threatening complication of paediatric malaria. Protracted production of pro-inflammatory cytokines promoting erythrophagocytosis and depressing erythropoiesis is thought to play an important role in SMA, which is characterized by a high TNF/IL-10 ratio. Whether this TNF/IL-10 imbalance results from an intrinsic incapacity of SMA patients to produce IL-10 or from an IL-10 unresponsiveness to infection is unknown. Monocytes and T cells are recognized as the main sources of TNF and IL-10 in vivo , but little is known about the activation status of those cells in SMA patients. Methods: The IL-10 and TNF production capacity and the activation phenotype of monocytes and T cells were compared in samples collected from 332 Ghanaian children with non-overlapping SMA (n= 108), cerebral malaria (CM) (n=144) or uncomplicated malaria (UM) (n=80) syndromes. Activation status of monocytes and T cells was ascertained by measuring HLA-DR + and/or CD69 + surface expression by flow cytometry. The TNF and IL-10 production was assessed in a whole-blood assay after or not stimulation with lipopolysaccharide (LPS) or phytohaemaglutinin (PHA) used as surrogate of unspecific monocyte and T cell stimulant. The number of circulating pigmented monocytes was also determined. Results: Monocytes and T cells from SMA and CM patients showed similar activation profiles with a comparable decreased HLA-DR expression on monocytes and increased frequency of CD69 + and HLA-DR + T cells. In contrast, the acute-phase IL-10 production was markedly decreased in SMA compared to CM ( P = .003) and UM ( P =.004). Although in SMA the IL-10 response to LPS-stimulation was larger in amplitude than in CM ( P =.0082), the absolute levels of IL-10 reached were lower ( P = .013). Both the amplitude and levels of TNF produced in response to LPS-stimulation were larger in SMA than CM ( P =.019). In response to PHA-stimulation, absolute levels of IL-10 produced in SMA were lower than in CM ( P =.005) contrasting with TNF levels, which were higher ( P =.001). Conclusions: These data reveal that SMA patients have the potential to mount efficient IL-10 responses and that the TNF/IL-10 imbalance may reflect a specific monocyte and T cell programming/polarization pattern in response to infection.Item Lead levels and related biochemical findings occurring in Ghanaian subjects occupationally exposed to lead.(1993) Ankrah, N.A.; Kamiya, Y.; Appiah-Oppong, R.; Acheampon, Y.A.; Addae, M.M.Blood and urine lead levels in relation to blood delta-aminolevulinic acid dehydratase (ALAD) activity and also blood and renal status were evaluated in lead smelters, automobile mechanics and gasoline retailers in the city of Accra, Ghana. Relationship between high blood lead levels (mean: 108 ug/dl) and low ALAD activity (mean: 74.3 units) indicating lead over exposure was found in the lead smelters. Non-toxic lead exposure was, however, noted in the automobile mechanics and the gasoline retailers. Their respective mean blood lead levels were 27.8 ug/dl (mean blood ALAD activity 212.5 units) and 8.6 ug/dl (ALAD: 239.9 units). Personal habits at the work place appear to play a major role in facilitating exposure to lead among all the three groups of workers in addition to lack of control measures at the work place of the lead smelters to protect them against lead exposure. Anaemia was found in 48% of the lead smelters, 12.5% of the gasoline retailers but in none of the automobile mechanics. When compared with lead free subjects (mean blood ALAD activity: 270.9 units), urine microalbumin was significantly (p < 0.01) raised in all the lead smelters suggesting that they may be prone to renal glomerular damage. Plasma creatinine, BUN and uric acid were raised in only one of the lead smelters. The data supports the establishment of blood ALAD activity level at 100 units or less as indication of excessive body lead.Item Plasma levels of Th1 and Th2 cytokines in Ghanaian children with vaccine-modified measles.(2003) Tetteh, J.K.A.; Addae, M.M.; Commey, J.O.O.; Ishiwada, N.; Yempewu, S.M.; Yamaguchi, S.; Ofori-Adjei, D.To understand the pathogenesis of vaccine-modified measles (VMM), we measured plasma levels of IFN-gamma and IL-2 (Th1 cytokines), IL-4 and IL-10 (Th2 cytokines), IL-12, TNF-alpha and TGF-beta1 in children with uncomplicated measles, who had anti-measles IgG antibodies and with a history of immunization on admission (day 0), day 14 and day 60. We compared these to levels in healthy, age-matched, immunized children. Plasma levels of IFN-gamma, IL-2 and IL-12 were significantly higher in VMM patients on day 0 compared to healthy controls (p = 0.023; p = 0.018; p = 0.001) respectively. In contrast, plasma IL-4 was lower in VMM patients on day 0 when compared to the controls (p = 0.009). Plasma levels of IL-12 remained consistently high on days 14 and 60 (p = 0.001; p = 0.04), whilst IL-10 levels fell significantly on the same days (p = 0.002; p = 0.001) respectively. Kinetically, IFN-gamma and IL-10 levels decreased consistently from day 0 to days 14 and 60 in VMM patients. In contrast, IL-4 levels increased from day 0 to day 14 and day 60. Our results therefore suggest that VMM is associated with an early up-regulation of Th1 cytokine production and a down-regulation of Th2 cytokine production. The strong Th1 response may be associated with the induction of IL-12 and memory cells, thus contributing to the early resolution of the infection and lack of complications.Item Population based reference intervals for common blood haematological and biochemical parameters in the Akuapem North District(Ghana Medical Journal 41(4): 160-6, 2007) Koram, K.; Addae, M.M.; Ocran, J.; Adu-Amankwah, S.; Rogers, W.; Nkrumah, F.Summary Objectives:: To estimate the reference intervals for commonly used blood haematology and biochemical parameters in an adult (18-55yrs) population of residents of Mampong Akuapem. DESIGN: This was a population based cross sectional study of a randomly selected sample of the adult population of Mampong. The sample was selected from an updated census list of the Mampong area. Results: Median values (95% range) for measured parameters were established as follows: Haemoglobin, (males) 14.2 g/dl (females) 12.0 g/dl Alanine aminotransferase (ALT), (female) 19.6 U/L (males) 26.1 U/L and Creatinine, (males) 108 mmol/L (females) 93 mmol/L. Conclusion: In comparison to reference values that are commonly used in Ghana, the haemoglobulin levels from this study were lower, and liver function parameters higher. This could be a result of genetic or environmental differences and calls for the need to establish site specific reference values applicable to our population.Item Surface marker patterns of T cells and expression of interleukin-2 receptor in measles infection(Acta Paediatrica Japonica, 1998) Addae, M.M.; Komada, Y.; Taniguchi, K.; Kamiya, T.; Osei-Kwasi, M.; Akanmori, B.D.; Nkrumah, F.K.The surface marker patterns of T cells of Ghanaian children during measles infection were studied and an attempt was made to demonstrate T cell activation and viability in vitro after activation in vivo by measles virus. The frequencies of CD4+ and CD8+ naive T cells in measles patients were high while their memory T cells were remarkably reduced with no sign of proliferation even at the acute phase of the illness. The reduction of memory T cells was prolonged during the convalescent phase (2 months after onset). The anti-CD3 monoclonal antibody-induced expression of interleukin-2 receptor alpha chain (IL-2R/CD25) was significantly suppressed; however, the addition of phorbol 12-myristate 13-acetate or ionomycin caused a remarkable recovery of CD25 expression. On simple culture, an appreciable proportion of T cells from measles patients died rapidly in contrast with only a few T cells from healthy controls doing so. The suppression of CD25 expression was still demonstrated during the convalescent phase of the disease. Taken together these results suggest unresponsiveness and activation-induced cell death of T cells during severe measles infection in Ghanaian children. Furthermore the prolonged abnormalities of T cells (i.e. decreased memory T cells and inhibition of CD25 expression during the convalescent phase) might be related to post-measles infection immunosuppressive status.Item Thl and Th2 Cytokine Profiles in Uncomplicated Measles Infection among a Group of Ghanain Children(University of Ghana, 2001-09) Addae, M.M.; Akanmori, B.D.; Duah, O.A.; Maddy, S.Q.; University of Ghana, College of Health Sciences, School of Biomedical and Allied Health Sciences, Department of Chemical PathologyMeasles remains a major severe infectious disease causing deaths of many children in most countries including Ghana. The disorder is associated with prolonged immunosuppression resulting in complications and mortality in children. Although attempts have been made to identify the specific immune functions altered during measles, the exact immune changes have not been fully characterized. The pro and anti-inflammatory response balances (Thl/Th2) are important in determining the pathogenesis and course of viral infections in general. CD4 mediated T cell responses to infectious agents may be dominated by type 1 or type 2 cells. Cell types are identified by the arrays of cytokine produced by each and have been clearly defined for mouse T cell clones. Similar distinctive patterns of cytokine production have been described for human T cell clones. Type 1 CD4 T cells secrete IL-2, IFN-γ and preferentially induce macrophage activation and delayed type hypersensitivity. Type 2 CD4 T cells produce IL-4, IL-5, IL-6 and IL-10, provide help for B cell responses and decrease macrophage activation. These subtypes of CD4 T cells are cross-regulatory. IFN-γ inhibits proliferation of type 2 CD4 cells whereas IL- 4 and EL-10 inhibit cytokine production by type 1 CD4 cells either directly or through their effects on macrophages. In this study, the profiles of Thl (IFN-γ, TNF-a) and Th2 (IL-4, IL-10, TGF|3) cytokine expression in vivo during uncomplicated measles among a group of Ghanaian children aged 12 years and below, mean age 6.2 ± 3.5 years were determined on days 0 (acute phase), 14 and 60 (convalescence stages). Results obtained were compared with age and sex-matched healthy controls. The results clearly showed high plasma levels of interleukin-4 (IL-4) a Th2 and an anti-inflammatory cytokine, early in the acute phase (day 0) of the disease, which declined by day 14, and day 60 post infection. Accompanying IL-4 up-regulation, Transforming growth factor β-1 (TGF-β) another anti-inflammatory cytokine also increased significantly and remained elevated in plasma samples of all patients throughout the study period (day 0, 14 and 60). The data however showed low levels of tumour necrosis factor alpha (TNF-α), a proinflammatory cytokine in the plasma samples of the patients at the acute and convalescent phases of the illness, and there was no significant difference observed between measles patients and healthy controls. Plasma levels of interleukin 12 (IL-12) and interleukin-2 (IL-2) were low in the study subjects on days 0, 14 and 60. IL-12 is critical for the orchestration of cellular immunity for the resolution of measles infection and in this study; IL-12 suppression was prolonged for 2 months after recovery from measles. Plasma levels of the Thl cytokine, interferon gamma (INF-γ) increased significantly (p<0.03) at the acute phase when compared with levels for the healthy controls. However, this increase was not maintained on days 14 and 60. Statistically significant reduction (p<0.05) in IL-10 levels was seen in days 14 and 60 samples of measles patients when compared with levels in plasma samples of healthy control group. Taken together, these data provide evidence of down-regulation of pro-inflammatory cytokine, TNF-α, and up-regulation of IL-4 an anti-inflammatory cytokine during measles infection. The mechanism by which type 2 CD4 T cells are preferentially activated during measles infection is not clear. Suggested contributing factors include genetic characteristics of the host, antigenic make-up of the pathogen, antigen dose and characteristics of the antigen presenting cell and its ability to signal T cells. The ability of measles virus to replicate in macrophages and to increase macrophage production of interleukin-1, could play a role in the preferential activation of type 1 CD4 cells that occurs during measles. This trend constitutes suppression of the immune system resulting in increased susceptibility of children to intracellular organisms and this could help to explain the many opportunistic infections associated with acute measles in Ghanaian children.Item Vaccine-modified measles in previously immunized children in Accra, Ghana: Clinical, virological and serological parameters.(2001) Ishiwada, N.; Addae, M.M.; Tetteh, J.K.A.; Yempewu, S.M.; Ofori-Adjei, D.; Kamiya, H.; Akanmori, B.D.Despite rapidly increasing measles immunization coverage, epidemics of measles occurred from January to March 2000 in some parts of Accra, the capital of Ghana. 44 cases of acute measles were diagnosed at three health facilities during the outbreaks, which we examined clinically and serologically. The peak incidence occurred among 6-12-year-olds, clinical symptoms were milder than the typical symptoms of measles, and fever was significantly less common. None of the cases developed complications and all recovered completely. Thirty-eight (86.4%) were tested serologically; IgM antibodies were detected in 73.7% and IgG antibodies in 84.2% during the acute phase. Milder symptoms in a significant number of cases with measles IgG antibodies suggest that these are vaccine-modified measles, attributable to waning antibodies and low circulation of wild type virus in an area of high vaccine coverage. Serological confirmation will be required for accurate diagnosis, if measles is to be eradicated or kept under control. It also seems likely that multiple dose immunization schedules will be needed in the future to maintain protective antibody levels and to protect children against measles in Ghana. This will eliminate the frequent outbreaks of measles involving immunized children.