Browsing by Author "Sarfo, B.Y."
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Item Burden of Malaria in Mobile Populations in Greater Accra Region(University of Ghana, 2016-07) Nouhoum , D.; Sarfo, B.Y.; University of Ghana, College of Health Sciences, School of Public HealthBackground: The burden of malaria in mobile populations is still less documented in sub-Saharan Africa. This study determined the prevalence of malaria among hawkers and long distance truck drivers in the Greater Accra region of Ghana. Method: A cross-sectional study using consecutive sampling method between June and July 2016 in Accra and Tema was used. The study population was Hawkers who roam in the street and long distance truck drivers. RDTs and two thick blood smears were made for each participant, stained with Giemsa and read using microscopy. The location and distribution of these mobile populations were collected using geospatial technology. Result: The overall prevalence of malaria was 15.1% and Plasmodium falciparum was responsible for all malaria infection. The malaria prevalence was 18.9% and 10.9% respectively among hawkers and truck drivers (p<0.05). The hawkers, the single and the no formal educated participants were more likely to get malaria than the long distance truck drivers (OR= 1.91, 95% CI 1.07–3.42), the married (OR= 1.94 95% CI 1.11– 3.40) and the educated participants (OR= 2.56 95% CI 1.10– 5.93) respectively. After controlling for other variables, marital status (OR= 2.60 95% CI 1.43– 4.73) and educational level (OR= 2.70 95% CI 1.08– 6.77) were statistically significantly associated with malaria. Conclusion: This study shows that the odds of getting malaria is high among hawkers and long distance truck drivers. The sociodemographic characteristics; locality, marital status, occupational work and educational level are significantly associated with malaria. The geospatial technology will make these mobile populations easy to reach for any malaria intervention.Item The cerebral-malaria-associated expression of RANTES, CCR3 and CCR5 in post-mortem tissue samples(Annals of Tropical Medicine and Parasitology, 2004) Sarfo, B.Y.; Singh, S.; Lillard, J.W.; Adjei, A.A.; Gyasi, R.K.; Armah, H.; Stiles, J.K.Item Cerebrospinal fluid and serum biomakers and cerebral malaria mortality in Ghanaian children(Malaria Journal, 2007) Armah, H.B.; Wilson, N.O.; Sarfo, B.Y.; Powell, M.D.; Bond, V.C.; Anderson, W.; Adjei, A.A.; Gyasi, R.K.; Tettey, Y.; Wiredu, E.K.; Tongren, J.E.; Udhayakumar, V.; Stiles, J.K.Background Plasmodium falciparum can cause a diffuse encephalopathy known as cerebral malaria (CM), a major contributor to malaria associated mortality. Despite treatment, mortality due to CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM and other forms of severe malaria is multi-factorial and appear to involve cytokine and chemokine homeostasis, inflammation and vascular injury/repair. Identification of prognostic markers that can predict CM severity will enable development of better intervention. Methods Postmortem serum and cerebrospinal fluid (CSF) samples were obtained within 2–4 hours of death in Ghanaian children dying of CM, severe malarial anemia (SMA), and non-malarial (NM) causes. Serum and CSF levels of 36 different biomarkers (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, Eotaxin, FGF basic protein, CRP, G-CSF, GM-CSF, IFN-γ, TNF-α, IP-10, MCP-1 (MCAF), MIP-1α, MIP-1β, RANTES, SDF-1α, CXCL11 (I-TAC), Fas-ligand [Fas-L], soluble Fas [sFas], sTNF-R1 (p55), sTNF-R2 (p75), MMP-9, TGF-β1, PDGF bb and VEGF) were measured and the results compared between the 3 groups. Results After Bonferroni adjustment for other biomarkers, IP-10 was the only serum biomarker independently associated with CM mortality when compared to SMA and NM deaths. Eight CSF biomarkers (IL-1ra, IL-8, IP-10, PDGFbb, MIP-1β, Fas-L, sTNF-R1, and sTNF-R2) were significantly elevated in CM mortality group when compared to SMA and NM deaths. Additionally, CSF IP-10/PDGFbb median ratio was statistically significantly higher in the CM group compared to SMA and NM groups. Conclusion The parasite-induced local cerebral dysregulation in the production of IP-10, 1L-8, MIP-1β, PDGFbb, IL-1ra, Fas-L, sTNF-R1, and sTNF-R2 may be involved in CM neuropathology, and their immunoassay may have potential utility in predicting mortality in CM.Item Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children(2007-11-12) Armah, H.B.; Wilson, N.O.; Sarfo, B.Y.; Powell, M.D.; Bond, V.C.; Anderson, W.; Adjei, A.A.; Gyasi, R.K.; Tettey, Y.; Wiredu, E.K.; Tongren, J.E.; Udhayakumar, V.; Stiles, J.K.Abstract Background Plasmodium falciparum can cause a diffuse encephalopathy known as cerebral malaria (CM), a major contributor to malaria associated mortality. Despite treatment, mortality due to CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM and other forms of severe malaria is multi-factorial and appear to involve cytokine and chemokine homeostasis, inflammation and vascular injury/repair. Identification of prognostic markers that can predict CM severity will enable development of better intervention. Methods Postmortem serum and cerebrospinal fluid (CSF) samples were obtained within 2–4 hours of death in Ghanaian children dying of CM, severe malarial anemia (SMA), and non-malarial (NM) causes. Serum and CSF levels of 36 different biomarkers (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, Eotaxin, FGF basic protein, CRP, G-CSF, GM-CSF, IFN-γ, TNF-α, IP-10, MCP-1 (MCAF), MIP-1α, MIP-1β, RANTES, SDF-1α, CXCL11 (I-TAC), Fas-ligand [Fas-L], soluble Fas [sFas], sTNF-R1 (p55), sTNF-R2 (p75), MMP-9, TGF-β1, PDGF bb and VEGF) were measured and the results compared between the 3 groups. Results After Bonferroni adjustment for other biomarkers, IP-10 was the only serum biomarker independently associated with CM mortality when compared to SMA and NM deaths. Eight CSF biomarkers (IL-1ra, IL-8, IP-10, PDGFbb, MIP-1β, Fas-L, sTNF-R1, and sTNF-R2) were significantly elevated in CM mortality group when compared to SMA and NM deaths. Additionally, CSF IP-10/PDGFbb median ratio was statistically significantly higher in the CM group compared to SMA and NM groups. Conclusion The parasite-induced local cerebral dysregulation in the production of IP-10, 1L-8, MIP-1β, PDGFbb, IL-1ra, Fas-L, sTNF-R1, and sTNF-R2 may be involved in CM neuropathology, and their immunoassay may have potential utility in predicting mortality in CM.Item Chemokine Mediators of Cerebral Malaria: A Comparative Study of the Role of Rantes in Murine and Human Cerebral Malaria(University of Ghana, 2004-09) Sarfo, B.Y.Although the involvement of cytokines and adhesion molecules in malaria-induced brain inflammation has been established, the role of chemokines and chemokine receptors remain unclear. This unexplained component of cerebral malaria (CM) pathology may be responsible for the heterogeneity in the observed features of CM and the difficulty in its characterization. RANTES (regulated on activation normal T cell expressed and secreted), a chemokine involved in the generation of inflammatory infiltrates plays a special role in the modulation of inflammation. Trafficking of inflammatory T helper 1 (THL) cells into the brain is mediated partly by RANTES interactions with c-c chemokine receptor 5 (CCR5) receptor. The main hypothesis of this study are:(a) RANTES and corresponding receptors mediate malaria induced brain immunopathogenesis (b) Blocking RANTES which is upregulated during malaria infection will abrogate or minimize the outcome of the disease. Studies were directed at i) Characterizing and analyzing the expression of RANTES and corresponding receptors CCR1, CCR3 and CCR5 in a mouse model of CM (SW mice/P.yoelii 17X) using eDNA microarray. RT-PCR and Western Blot analyses ii) Evaluating effect of P.yoelii 17X infection on mouse brain by electron microscopy and immunohistological analyses iii) Evaluating expression of RANTES and receptors in cerebellum, cerebrum, brain stem and hippocampus of post-mortem CM and non-malaria (NM) tissue samples using RT-PCR and Western Blot analyses iv) Comparing and contrasting levels of RANTES in plasma of rodent malaria model and malaria-positive human subjects using ELISA v) Determine the functional role of RANTES by anti-RANTES antibody blocking experiment using P.yeolii 17X infected mice. Transcriptional analyses results indicate significant upregulation of chemokines; macrophage inflammatory protein-2a(MIP-2a.), monocyte chemotactic protein-1 (MCP-1) and RANTES chemokine receptors; CCR1, CCR3, and CCR5, adhesion molecules; platelet endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule-l (VCAM-l) and cytokines; intereferon-gamma (INF-y), tumour necrosis factor-alpha (TNF-a) and interleukin-12 (IL-12) at peak parasitemia during P.yoelii 17X infection. Western Blot analysis revealed upregulation of RANTES protein in P.yoelii 17X infected mouse brain. Ultrastructural analysis showed that P.yoelii 17X infection induces perivascular oedema in cerebellum in mouse brain at peak parasitemia. lmmunohistological analysis demonstrates high immunoreactivity of glial fibrillary acidic protein (GFAP) ill P.yoelii l7X infected mouse brain. RANTES, CCR3 and CCR5 but not CCR1 mRNA are significantly upregulated in the cerebellum and cerebrum (P < 0.0001) in CM than NM samples. There were no changes in the expression of CCR1, CCR3 and CCR5 mRNA in brain stem and hippocampus of CM and NM. RANTES mRNA expression in cerebellum and cerebrum is highly significant(p < 0.0001) compared with the brain stem(p = 0.0018) and hippocampus (p=0.0027) in CM group. CCR5 and RANTES proteins were significantly upregulated in cerebellum (P < 0.0013 for CCR5, P < 0.0001 for RANTES) and cerebrum (P < 0.0124 for CCR5, P < 0.0001 for RANTES) but not brain stem and hippocampus of CM than in NM. Western Blot analysis could not detest CCR3 protein RANTES was significantly upregulated in plasma of murine malaria model and malaria positive subjects compared with controls. RANTES concentration in plasma correlated with P. falciparum infection. At day of sacrifice. level of parasitemia (4.2x 10^6/ml ±O.2) in mock antibody treated mice was higher (P < 0.05) than in mice in which RANTES was blocked with anti-RANTES antibody(1.2 x 10^6/ml ± 0.2). Anti-RANTES antibody treated mice survived longer (14 days) than mock antibody treated mice (10 days). This is the first temporal study of murine malaria associated RANTES and receptors CCR1, CCR3 and CCR5 expression. P.yoelii 17X murine malaria model is useful in characterizing differentially expressed genes associated with human clinical malaria. There is an association of RANTES expression in malaria-induced brain immunopathogenesis and endothelial lesions in infected mice. Cerebellum and cerebrum in humans were the focal points for increased malaria-induced RANTES and CCR5 expression. Active sequestration of infected red blood cells (IRBCs) and platelets in addition to leukocytes in these regions of the brain could exacerbate CM immnopathology. Blocking of RANTES decreased parasitemia and mortality associated with P.yoelii 17X infection.Item Factors Associated with Care Continuum of Hiv/Aids Patients Receiving Antiretroviral Therapy at the International Health Care Center (Ihcc), Ghana(University of Ghana, 2016-07) Korley, A.; Sarfo, B.Y.; University of Ghana, College of Health Sciences School of Public HealthBackground: The advancement through the HIV Care Cascade, from HIV testing to permanent retention in Antiretroviral Therapy (ART) Care and treatment programs, is vital to the success of HIV treatment and prevention efforts. However, persons are lost to follow-up at each stage of the Continuum and little is known about the factors contributing to attrition at these stages in Ghana. This study determined factors associated with Care Continuum of HIV/AIDS patients receiving antiretroviral therapy between 2011 and 2015 at the International Health Care Center (IHCC). Method: This was a cross-sectional study. 152 participants were conveniently sampled and data extracted from their medical records and supplementary closed-ended interviews were performed. Data were analyzed using STATA and frequencies, proportions, percentages, chi square and regression analyses were performed. Results: Among persons living with HIV/AIDS who visit the IHCC, 79% were tested positive and linked to care. Retention among study participants receiving care at the IHCC was 53% of which 42% had improvement in their CD4 count over the period of the study. The chi-square test revealed that marital status and drug line (drug related factor) were significantly associated with retention. Age and drug line were also significantly associated with CD4 count improvement. Regression analysis showed that the age group 35-44 years participants are most likely to achieve improvement in CD4 count (AOR=34.97, 95% CI 2.22-550.81; p<0.05) and the first drug line choice was significantly associated with improvement in CD4 count (AOR= 0.17, 95% CI 0.04-0.63; p<0.05). Conclusion: Out of 1127 participants who have been tested and linked to care at IHCC, 53% of them were retained in care and 42% had improvement in their CD4 count. Marital status and choice of drug line were associated with retention in care while age and choice of drug line were associated with improvement in CD4 count.Item Plasmodium yoelii17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellum(2005-12-16) Sarfo, B.Y.; Armah, H.B.; Irune, I.; Adjei, A.A.; Olver, C.S.; Singh, S.; Lillard, J.W.; Stiles, J.K.Abstract Background Malaria afflicts 300–500 million people causing over 1 million deaths globally per year. The immunopathogenesis of malaria is mediated partly by co mplex cellular and immunomodulator interactions involving co-regulators such as cytokines and adhesion molecules. However, the role of chemokines and their receptors in malaria immunopathology remains unclear. RANTES (Regulated on Activation Normal T-Cell Expressed and Secreted) is a chemokine involved in the generation of inflammatory infiltrates. Recent studies indicate that the degradation of cell-cell junctions, blood-brain barrier dysfunction, recruitment of leukocytes and Plasmodium-infected erythrocytes into and occlusion of microvessels relevant to malaria pathogenesis are associated with RANTES expression. Additionally, activated lymphocytes, platelets and endothelial cells release large quantities of RANTES, thus suggesting a unique role for RANTES in the generation and maintenance of the malaria-induced inflammatory response. The hypothesis of this study is that RANTES and its corresponding receptors (CCR1, CCR3 and CCR5) modulate malaria immunopathogenesis. A murine malaria model was utilized to evaluate the role of this chemokine and its receptors in malaria. Methods The alterations in immunomodulator gene expression in brains of Plasmodium yoelii 17XL-infected mice was analysed using cDNA microarray screening, followed by a temporal comparison of mRNA and protein expression of RANTES and its corresponding receptors by qRT-PCR and Western blot analysis, respectively. Plasma RANTES levels was determined by ELISA and ultrastructural studies of brain sections from infected and uninfected mice was conducted. Results RANTES (p < 0.002), CCR1 (p < 0.036), CCR3 (p < 0.033), and CCR5 (p < 0.026) mRNA were significantly upregulated at peak parasitaemia and remained high thereafter in the experimental mouse model. RANTES protein in the brain of infected mice was upregulated (p < 0.034) compared with controls. RANTES plasma levels were significantly upregulated; two to three fold in infected mice compared with controls (p < 0.026). Some d istal microvascular endothelium in infected cerebellum appeared degraded, but remained intact in controls. Conclusion The upregulation of RANTES, CCR1, CCR3, and CCR5 mRNA, and RANTES protein mediate inflammation and cellular degradation in the cerebellum during P. yoelii 17XL malaria.