We follow our cow...and forget our home': Movement, survival, and Fulani identity in Greater Accra, Ghana.

We follow our cow and forget our home'. This statement encapsulates the problems that this thesis addresses in relation to the three interdependent themes of identity, movement and survival. This study is concerned with Fulani identities and mobility in Greater Accra, Ghana. It is ultimately about Fulani survival across space and through time. It involves an understanding of where people are coming from, where they have travelled to and the environments in which they have grown up, been educated, married, borne children and worked. The units of analysis are the lives, stories and experiences of individuals, as well as the communities and ultimately ethnic group of which they form a part. The account thus addresses the 'personal troubles' of individual women and men, both young and old, as well as wider 'public issues' taken up by the Ghanaian state and press. These issues are also observed to be the subject of debate and concern in the Fulani community in Greater Accra. This thesis concerns itself with the sites and circumstances in which Fulani consider themselves to be the same or different. The markers of Fulani identity, as recognized by Fulani and non-Fulani alike, are examined. The factors are investigated that allow them, as a distinct ethnic category, to maintain and perpetuate this identity and viability in Greater Accra. The analogy of 'construction sites' is useful for considering these different, explicit and implicit events and recurring processes, through which people reproduce themselves as Fulani (of various kinds). These sites are locations as well as contexts of action. They are social circumstances (with personnel, power relations, procedures etc.) such as ethnic associations, public gatherings and common rites of passage. The recurring processes include genealogical reckoning of kinship and endogamous marriage transactions, and the ways in which ties of descent and filiation are used to enhance individual survival and family development goals

Integrating informatics tools and portable sequencing technology for rapid detection of resistance to anti-tuberculous drugs

BACKGROUND: Mycobacterium tuberculosis resistance to anti-tuberculosis drugs is a major threat to global public health. Whole genome sequencing (WGS) is rapidly gaining traction as a diagnostic tool for clinical tuberculosis settings. To support this informatically, previous work led to the development of the widely used TBProfiler webtool, which predicts resistance to 14 drugs from WGS data. However, for accurate and rapid high throughput of samples in clinical or epidemiological settings, there is a need for a stand-alone tool and the ability to analyse data across multiple WGS platforms, including Oxford Nanopore MinION. RESULTS: We present a new command line version of the TBProfiler webserver, which includes hetero-resistance calling and will facilitate the batch processing of samples. The TBProfiler database has been expanded to incorporate 178 new markers across 16 anti-tuberculosis drugs. The predictive performance of the mutation library has been assessed using > 17,000 clinical isolates with WGS and laboratory-based drug susceptibility testing (DST) data. An integrated MinION analysis pipeline was assessed by performing WGS on 34 replicates across 3 multi-drug resistant isolates with known resistance mutations. TBProfiler accuracy varied by individual drug. Assuming DST as the gold standard, sensitivities for detecting multi-drug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) were 94% (95%CI 93-95%) and 83% (95%CI 79-87%) with specificities of 98% (95%CI 98-99%) and 96% (95%CI 95-97%) respectively. Using MinION data, only one resistance mutation was missed by TBProfiler, involving an insertion in the tlyA gene coding for capreomycin resistance. When compared to alternative platforms (e.g. Mykrobe predictor TB, the CRyPTIC library), TBProfiler demonstrated superior predictive performance across first- and second-line drugs. CONCLUSIONS: The new version of TBProfiler can rapidly and accurately predict anti-TB drug resistance profiles across large numbers of samples with WGS data. The computing architecture allows for the ability to modify the core bioinformatic pipelines and outputs, including the analysis of WGS data sourced from portable technologies. TBProfiler has the potential to be integrated into the point of care and WGS diagnostic environments, including in resource-poor settings

A Phase I Study of Ad5-GUCY2C-PADRE in Stage I and II Colon Cancer Patients

Background Ad5-GUCY2C-PADRE is a replication-deficient human type 5 recombinant adenovirus (Ad5) vaccine encoding guanylyl cyclase C (GUCY2C) fused to the PAn DR Epitope (PADRE). GUCY2C, a paracrine hormone receptor producing the second messenger cyclic GMP (cGMP), is selectively expressed by intestinal epithelial cells and a subset of hypothalamic neurons, but not other tissues. Importantly, GUCY2C is over-expressed in nearly all primary and metastatic human colorectal tumors. Preclinical studies in mice demonstrated selective tolerance of GUCY2C-specific CD4+ T cells, but not CD8+ T or B cells, necessitating inclusion of the exogenous CD4+ T helper cell epitope PADRE to maximize GUCY2C-specific CD8+ T-cell and antibody responses and antitumor efficacy, without autoimmunity. Patients and Methods This is an open-label, single arm “proof-of-concept” study evaluating a single dose level of Ad5-GUCY2C-PADRE as a vaccine for surgically-treated, node-negative colon cancer subjects (NCT01972737). Patients received a single intramuscular administration of 1011 Ad5-GUCY2C-PADRE viral particles. Safety and immunomonitoring were examined at 30, 90 and 180 days following vaccination. Primary objectives were to determine the safety, tolerability, and toxicity of Ad5-GUCY2C-PADRE and to determine whether Ad5- GUCY2C-PADRE induces GUCY2C-specific immune responses. The study employed a joint efficacy-toxicity design and included stopping rules for either efficacy or toxicity.Results here were obtained during the planned interim analysis following accrual of 10 subjects. Results The vaccine was well tolerated, producing only mild adverse events (AEs). Short-lived injection site pain/swelling, body aches, and chills were the most commonly observed AEs and occurred in 30-40% of subjects. GUCY2C-specific antibody and T-cell responses were observed in a subset of subjects. Consistent with preclinical mouse data, T-cell responses were composed of CD8+, but not CD4+, T cells. Importantly, GUCY2C-specific responses occurred only in subjects with low Ad5 neutralizing antibody (NAb) titers at the time of vaccination, suggesting that pre-existing Ad5 immunity limits Ad5-GUCY2C-PADRE immunogenicity. Conclusions Interim analysis of 10 subjects receiving Ad5-GUCY2C-PADRE demonstrates proof-of-concept that GUCY2C is immunogenic in humans and that GUCY2C-directed vaccination is safe. Moreover, the presence of GUCY2C-specific antibody and CD8+ T-cell, but not CD4+ T-cell, responses is consistent with selective CD4+ T-cell tolerance observed in mouse models. These data establish GUCY2C as a safe and immunogenic target for immunotherapy in cancer patients. Poster presented at: Immunotherapy of Cancer (SITC) 30th Annual Meeting in National Harbor Maryland.https://jdc.jefferson.edu/petposters/1001/thumbnail.jp

The psychosocial burden of women seeking treatment for breast and cervical cancers in Ghana's major cancer hospitals.

BackgroundBreast and cervical cancers remain the most common cancers and the leading cause of cancer deaths in Ghana. Non-communicable diseases such as cancers, have been associated with psychological burdens such as anxiety and depression disorders as well as severe mental disorders such as bipolar disorder. As such the World Health Organisation has noted that mental health and well-being are crucial in reducing the NCD burden.MethodsA convergent mixed method approach was used to ascertain the psychosocial burden of breast and cervical cancer patients who sought treatment in three major cancer hospitals in Ghana. Primary data were collected using a questionnaire and an interview guide from 298 breast and cervical cancer patients seeking treatment at the Korle-Bu and Komfo Anokye Teaching Hospitals as well as the Sweden Ghana Medical Centre. Qualitative analysis was done using thematic content analysis while quantitative analysis was done using logistic regression.ResultsThe findings of the study showed that patients not only battled with psychological burdens such as anxiety, depression, pain, stigma, fear of death and loss of spouses but also struggled with physical, social, and dietary restrictions. Patients with low educational levels and income status, retired or unemployed, and/or had larger household sizes suffered more psychosocial burdens.ConclusionThere is a need for liaison psychiatrists and health psychologists to assist oncologists to provide psychological support such as free and routine counselling services for cancer patients and their caregivers. Educational campaigns on mainstream and social media need to be intensified to demystify the stigma surrounding cancers in Ghana

Phase II mixed methods’ feasibility cluster randomised controlled trial of a novel community-based enhanced care intervention to improve person-centred outcomes for people living with HIV in Ghana

Person-centred care (PCC) for people living with HIV (PLWH) is a global goal for WHO and the UNAIDS strategy. We aimed to develop a novel person-centred intervention for community providers, test the feasibility of participant recruitment and retention, intervention delivery and to establish acceptability. Findings from qualitative interviews with PLWH and healthcare professionals were mapped onto a PCC theory in an expert intervention development workshop. A parallel feasibility cluster randomised controlled trial (cRCT) was conducted. We randomly assigned clusters (1:1) either to intervention or to standard care. The primary outcome was trial recruitment and retention. We screened 83 PLWH, enrolled 60 with 30 allocated to each arm. Recruitment and retention rates were 87% and 97%, respectively. Potential effect size achieved at final timepoint: a measure of person-centred outcomes [0.7 (95% CI 0.17–1.23) p < 0.001]; MOSHIV [0.7 (95% CI 0.17–1.23) p < 0.001]; Patient Experience Questionnaire [0.8 (95% CI 0.27–1.31) p < 0.001]; CARE Measure [1.0 (95% CI 0.45–1.55) p < 0.001], POSITIVE OUTCOMES [0.7 (95% CI 0.17–1.23) p < 0.001]. Post-trial interviews revealed general acceptability of the intervention. The results confirm the feasibility and justify a definitive cRCT of the enhanced care intervention to improve person-centred outcomes for PLWH.Trial registration number ISRCTN13630241

Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance

Abstract Background Continuing evolution of the Mycobacterium tuberculosis (Mtb) complex genomes associated with resistance to anti-tuberculosis drugs is threatening tuberculosis disease control efforts. Both multi- and extensively drug resistant Mtb (MDR and XDR, respectively) are increasing in prevalence, but the full set of Mtb genes involved are not known. There is a need for increased sensitivity of genome-wide approaches in order to elucidate the genetic basis of anti-microbial drug resistance and gain a more detailed understanding of Mtb genome evolution in a context of widespread antimicrobial therapy. Population structure within the Mtb complex, due to clonal expansion, lack of lateral gene transfer and low levels of recombination between lineages, may be reducing statistical power to detect drug resistance associated variants. Results To investigate the effect of lineage-specific effects on the identification of drug resistance associations, we applied genome-wide association study (GWAS) and convergence-based (PhyC) methods to multiple drug resistance phenotypes of a global dataset of Mtb lineages 2 and 4, using both lineage-wise and combined approaches. We identify both well-established drug resistance variants and novel associations; uniquely identifying associations for both lineage-specific and -combined GWAS analyses. We report 17 potential novel associations between antimicrobial resistance phenotypes and Mtb genomic variants. Conclusions For GWAS, both lineage-specific and -combined analyses are useful, whereas PhyC may perform better in contexts of greater diversity. Unique associations with XDR in lineage-specific analyses provide evidence of diverging evolutionary trajectories between lineages 2 and 4 in response to antimicrobial drug therapy

Hospitalizations among children with sickle cell disease enrolled in the Kumasi Sickle Cell Pan African Consortium (SPARCo) database: A cross sectional study

Abstract Background and Aims Sickle cell disease (SCD) is the commonest monogenic haemolytic disorder in Africa. Despite strides made in its management, a significant proportion of patients are hospitalized from the various complications of the disease. This study set out to describe the main causes and outcomes of hospitalizations among pediatric patients with SCD. Methods A cross‐sectional study was conducted at the Pediatric Emergency Unit of Komfo Anokye Teaching Hospital within a period of 12 months to recruit pediatric SCD patients. This study looked at causes of admission, length of hospital stay (LOS), and outcome of admission. Results Of the 201 SCD patients recruited, 57.2% were males and majority were of SCD‐SS phenotype 83.1%. The median age was 6 years. The three leading causes of hospitalization were Vaso‐occlusive pain events (VOPE) (39.8%), acute chest syndrome (ACS) (25.9%), and infections (12.4%). Ten (5.0%) of the patients presented with a stroke. High admissions were observed in June (12.4%) and November (16.9%). The median (interquartile range [IQR]) LOS was 6 days (IQR: 4–10). Six (3.0%) of the patients died from complications of the disease during hospitalization. Conclusion VOPE, ACS, infections, and acute anaemia from hyperhaemolysis were observed as the most common causes of admissions among SCD patients. A good outcome of discharge was seen in most of the patients that were hospitalized with a median length of stay of 6 days. This study also strengthens the importance of a good SCD database with patient follow‐ups for better outcomes in SCD patients