Browsing by Author "Enimil, A."
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Item Autophagy gene variant IRGM -261T contributes to protection from tuberculosis caused by Mycobacterium tuberculosis but not by M. africanum strains(2009-09) Intemann, C.D.; Thye, T.; Niemann, S.; Browne, E.N.L.; Chinbuah, M.A.; Enimil, A.; Gyapong, J.; Osei, I.; Owusu-Dabo, E.; Helm, S.; Rüsch-Gerdes, S.; Horstmann, R.D.; Meyer, C.G.The human immunity-related GTPase M (IRGM) has been shown to be critically involved in regulating autophagy as a means of disposing cytosolic cellular structures and of reducing the growth of intracellular pathogens in vitro. This includes Mycobacterium tuberculosis, which is in agreement with findings indicating that M. tuberculosis translocates from the phagolysosome into the cytosol of infected cells, where it becomes exposed to autophagy. To test whether IRGM plays a role in human infection, we studied IRGM gene variants in 2010 patients with pulmonary tuberculosis (TB) and 2346 unaffected controls. Mycobacterial clades were classified by spoligotyping, IS6110 fingerprinting and genotyping of the pks1/15 deletion. The IRGM genotype -261TT was negatively associated with TB caused by M. tuberculosis (OR 0.66, CI 0.52-0.84, P nominal 0.0009, P corrected 0.0045) and not with TB caused by M. africanum or M. bovis (OR 0.95, CI 0.70-1.30. P 0.8). Further stratification for mycobacterial clades revealed that the protective effect applied only to M. tuberculosis strains with a damaged pks1/15 gene which is characteristic for the Euro-American (EUAM) subgroup of M. tuberculosis (OR 0.63, CI 0.49-0.81, Pnominal 0.0004, Pcorrected 0.0019). Our results, including those of luciferase reporter gene assays with the IRGM variants -261C and -261T, suggest a role for IRGM and autophagy in protection of humans against natural infection with M. tuberculosis EUAM clades. Moreover, they support in vitro findings indicating that TB lineages capable of producing a distinct mycobacterial phenolic glycolipid that occurs exclusively in strains with an intact pks1/15 gene inhibit innate immune responses in which IRGM contributes to the control of autophagy. Finally, they raise the possibility that the increased frequency of the IRGM -261TT genotype may have contributed to the establishment of M. africanum as a pathogen in the West African population.Item Autophagy Gene Variant IRGM 2261T Contributes to Protection from Tuberculosis Caused by Mycobacterium tuberculosis but Not by M. africanum Strains(PLoS Pathogens, 2009) Intemann, C.D.; Thye, T.; Niemann, S.; Browne, E.N.L.; Chinbuah, M.A.; Enimil, A.; Gyapong, J.O.; Osei, I.; Owusu-Dabo, E.; Helm, S.; Rüsch-Gerdes, S.; Horstmann, R.D.; Meyer, C.G.The human immunity-related GTPase M (IRGM) has been shown to be critically involved in regulating autophagy as a means of disposing cytosolic cellular structures and of reducing the growth of intracellular pathogens in vitro. This includes Mycobacterium tuberculosis, which is in agreement with findings indicating that M. tuberculosis translocates from the phagolysosome into the cytosol of infected cells, where it becomes exposed to autophagy. To test whether IRGM plays a role in human infection, we studied IRGM gene variants in 2010 patients with pulmonary tuberculosis (TB) and 2346 unaffected controls. Mycobacterial clades were classified by spoligotyping, IS6110 fingerprinting and genotyping of the pks1/15 deletion. The IRGM genotype 2261TT was negatively associated with TB caused by M. tuberculosis (OR 0.66, CI 0.52– 0.84, Pnominal 0.0009, Pcorrected 0.0045) and not with TB caused by M. africanum or M. bovis (OR 0.95, CI 0.70–1.30. P 0.8). Further stratification for mycobacterial clades revealed that the protective effect applied only to M. tuberculosis strains with a damaged pks1/15 gene which is characteristic for the Euro-American (EUAM) subgroup of M. tuberculosis (OR 0.63, CI 0.49– 0.81, Pnominal 0.0004, Pcorrected 0.0019). Our results, including those of luciferase reporter gene assays with the IRGM variants 2261C and 2261T, suggest a role for IRGM and autophagy in protection of humans against natural infection with M. tuberculosis EUAM clades. Moreover, they support in vitro findings indicating that TB lineages capable of producing a distinct mycobacterial phenolic glycolipid that occurs exclusively in strains with an intact pks1/15 gene inhibit innate immune responses in which IRGM contributes to the control of autophagy. Finally, they raise the possibility that the increased frequency of the IRGM 2261TT genotype may have contributed to the establishment of M. africanum as a pathogen in the West African population.Item Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2.(2010-09) Thye, T.; Vannberg, F.O.; Wong, S.H.; Owusu-Dabo, E.; Osei, I.; Gyapong, J.; Sirugo, G.; Sisay-Joof, F.; Enimil, A.; Chinbuah, M.A.; Floyd, S.; Warndorff, D.K.; Sichali, L.; Malema, S.; Crampin, A.C.; Ngwira, B.; Teo, Y.Y.; Small, K.; Rockett, K.; Kwiatkowski, D.; Fine, P.E.; Hill, P.C.; Newport, M.; Lienhardt, C.; Adegbola, R.A.; Corrah, T.; Ziegler, A.; African TB Genetics Consortium; Wellcome Trust Case Control Consortium; Morris, A.P.; Meyer, C.G.; Horstmann, R.D.; Hill, A.V.We combined two tuberculosis genome-wide association studies from Ghana and The Gambia with subsequent replication in a combined 11,425 individuals. rs4331426, located in a gene-poor region on chromosome 18q11.2, was associated with disease (combined P = 6.8 x 10(-9), odds ratio = 1.19, 95% CI = 1.13-1.27). Our study demonstrates that genome-wide association studies can identify new susceptibility loci for infectious diseases, even in African populations, in which levels of linkage disequilibrium are particularly low.Item Highly active antiretroviral therapy adherence among perinatally infected HIV adolescents at a teaching hospital in Ghana(AIDS Care - Psychological and Socio-Medical Aspects of AIDS/HIV, 2018-07) Anokye-Kumatia, A.B.; Enimil, A.; Afriyie, D.K.; Tetteh, R.; Mensah, N.K.; Amo, A.A.; Gariba, B.B.; Amponsah, S.Increased accessibility to Antiretroviral Therapy (ART) has resulted in the decline of deaths among children with Perinatally Infected Human Immunodeficiency Virus (PIHIV). Their adherence to Highly Active ART (HAART) is vital for their survival and quality of life. This study aimed at determining HAART medication adherence among adolescents with PIHIV. The study was cross-sectional conducted from September 2015 to January 2016 at a teaching hospital in Ghana. It involved 106 adolescents aged 10-20 years. Morisky's eight-item medication adherence scale was adapted and used to determine the adherence level. Factors influencing adherence were also determined by interviewing the adolescents. EpiData 3.1 and Stata version 12 were used for data entry and analysis respectively. There was low adherence in 76.4% of the adolescents, and the HAART regimen associated with high medication adherence was tenofovir, lamivudine and efavirenz combinations (p = .011). Forgetfulness (p = .001) and inability to come for refill (p = .013) were the main factors associated with low adherence. However adherence was not significantly associated with a lack of medication supply or stigmatization. Addressing the modifiable factors found in this study to be associated with low adherence are essential interventions for their long-term quality of life.Item HIV knowledge, stigma, and illness beliefs among pediatric caregivers in Ghana who have not disclosed their child's HIV status(AIDS Care, 2015-11) Paintsil, E.; Renner, L.; Antwi, S.; Dame, J.; Enimil, A.; Ofori-Atta, A.; Alhassan, A.; Ofori, I.P.; Cong, X.; Kyriakides, T.; Reynolds, N.R.The majority of HIV-infected children in sub-Saharan Africa have not been informed of their HIV status. Caregivers are reluctant to disclose HIV status to their children because of concern about the child’s ability to understand, parental sense of guilt, and fear of social rejection and isolation. We hypothesized that the low prevalence of pediatric HIV disclosure in Ghana is due to lack of accurate HIV information and high HIV stigma among caregivers. This is a preliminary analysis of baseline data of an HIV pediatric disclosure intervention study in Ghana (“Sankofa”). “Sankofa” – is a two-arm randomized controlled clinical trial comparing disclosure intervention plus usual care (intervention arm) vs usual care (control arm) at Korle-Bu Teaching Hospital (KBTH; control arm) and Komfo-Anokye Teaching Hospital (KATH; intervention arm). We enrolled HIV-infected children, ages 7–18 years who do not know their HIV status, and their caregivers. Baseline data of caregivers included demographic characteristics; Brief HIV Knowledge Questionnaire (HIV-KQ-18); Brief Illness Perception Questionnaire; and HIV Stigma Scale. Simple and multivariable linear regression analyses were used to assess the relationship between caregiver characteristics and HIV knowledge, stigma, and illness perception. Two hundred and ninety-eight caregivers were enrolled between January 2013 and July 2014 at the two study sites; KBTH (n = 167) and KATH (n = 131). The median age of caregivers was 41 years; 80.5% of them were female and about 60% of caregivers were HIV-positive. Seventy-eight percent of caregivers were self-employed with low household income. In both unadjusted and adjusted analyses, HIV negative status and lower level of education were associated with poor scores on HIV-KQ. HIV positive status remained significant for higher level of stigma in the adjusted analyses. None of the caregiver’s characteristics predicted caregiver’s illness perception. Intensification of HIV education in schools and targeted community campaigns are needed.Item SANKOFA: a multisite collaboration on paediatric HIV disclosure in Ghana(AIDS, 2015-06) Reynolds, N.R.; Ofori-Atta, A.; Lartey, M.; Renner, L.; Antwi, S.; Enimil, A.; Catlin, A.C.; Fernando, S.; Kyriakides, T.C.; Paintsil, E.With the scale-up of effective antiretroviral therapy in resource-limited settings, many HIV-infected children are now able to survive into adulthood. To achieve this potential, children must navigate normative developmental processes and challenges while living with an unusually complex, stigmatizing, potentially fatal chronic illness and meeting the demands of treatment. Yet many of these children, especially preadolescents, do not know they are HIV-infected. Despite compelling evidence supporting the merits of informing children of their HIV status, there has been little emphasis on equipping the child’s caregiver with information and skills to promote disclosure, particularly, when the caregiver faces a variety of sociocultural barriers and is reluctant to do so. In this study, we present the background, process and methods for a first of its kind collaboration that is examining the efficacy of an intervention developed to facilitate the engagement of caregivers in the process of disclosure in a manner suitable to the sociocultural context and developmental age and needs of the child in Ghana. We also report preliminary data that supported the design of the intervention approach and currently available domains of the data system. Finally, we discuss challenges and implications for future research.Item Variant G57E of Mannose Binding Lectin Associated with Protection against Tuberculosis Caused by Mycobacterium africanum but not by M. tuberculosis(PLoS ONE, 2011-06) Thye, T.; Niemann, S.; Walter, K.; Homolka, S.; Intemann, C.D.; Chinbuah, M.A.; Enimil, A.; Gyapong, J.O.; Owusu-Dabo, E.; Rüsch-Gerdes, S.; Horstmann, R.D.; Ehlers, S.; Meyer, C.G.Structural variants of the Mannose Binding Lectin (MBL) cause quantitative and qualitative functional deficiencies, which are associated with various patterns of susceptibility to infectious diseases and other disorders. We determined genetic MBL variants in 2010 Ghanaian patients with pulmonary tuberculosis (TB) and 2346 controls and characterized the mycobacterial isolates of the patients. Assuming a recessive mode of inheritance, we found a protective association between TB and the MBL2 G57E variant (odds ratio 0.60, confidence interval 0.4–0.9, P 0.008) and the corresponding LYQC haplotype (Pcorrected 0.007) which applied, however, only to TB caused by M. africanum but not to TB caused by M. tuberculosis. In vitro, M.africanum isolates bound recombinant human MBL more efficiently than did isolates of M. tuberculosis. We conclude that MBL binding may facilitate the uptake of M. africanum by macrophages, thereby promoting infection and that selection by TB may have favoured the spread of functional MBL deficiencies in regions endemic for M. africanum