Transforming Parkinson's Care in Africa (TraPCAf): protocol for a multimethodology National Institute for Health and Care Research Global Health Research Group project.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder and, according to the Global Burden of Disease estimates in 2015, was the fastest growing neurological disorder globally with respect to associated prevalence, disability, and deaths. Information regarding the awareness, diagnosis, phenotypic characteristics, epidemiology, prevalence, risk factors, treatment, economic impact and lived experiences of people with PD from the African perspective is relatively sparse in contrast to the developed world, and much remains to be learned from, and about, the continent. METHODS: Transforming Parkinson's Care in Africa (TraPCAf) is a multi-faceted, mixed-methods, multi-national research grant. The study design includes multiple sub-studies, combining observational (qualitative and quantitative) approaches for the epidemiological, clinical, risk factor and lived experience components, as appropriate, and interventional methods (clinical trial component). The aim of TraPCAf is to describe and gain a better understanding of the current situation of PD in Africa. The countries included in this National Institute for Health and Care Research (NIHR) Global Health Research Group (Egypt, Ethiopia, Ghana, Kenya, Nigeria, South Africa and Tanzania) represent diverse African geographies and genetic profiles, with differing resources, healthcare systems, health and social protection schemes, and policies. The research team is composed of experts in the field with vast experience in PD, jointly led by a UK-based and Africa-based investigator. DISCUSSION: Despite the increasing prevalence of PD globally, robust data on the disease from Africa are lacking. Existing data point towards the poor awareness of PD and other neurological disorders on the continent and subsequent challenges with stigma, and limited access to affordable services and medication. This multi-site study will be the first of its kind in Africa. The data collected across the proposed sub-studies will provide novel and conclusive insights into the situation of PD. The selected country sites will allow for useful comparisons and make results relevant to other low- and middle-income countries. This grant is timely, as global recognition of PD and the public health challenge it poses builds. The work will contribute to broader initiatives, including the World Health Organization's Intersectoral global action plan on epilepsy and other neurological disorders. TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN77014546 .

Renal health after long-term exposure to tenofovir disoproxil fumarate (TDF) in HIV/HBV positive adults in Ghana.

OBJECTIVES: The study assessed markers of renal health in HIV/HBV co-infected patients receiving TDF-containing antiretroviral therapy in Ghana. METHODS: Urinary protein-to-creatinine ratio (uPCR) and albumin-to-protein ratio (uAPR) were measured cross-sectionally after a median of four years of TDF. At this time, alongside extensive laboratory testing, patients underwent evaluation of liver stiffness and blood pressure. The estimated glomerular filtration rate (eGFR) was measured longitudinally before and during TDF therapy. RESULTS: Among 101 participants (66% women, median age 44 years, median CD4 count 572 cells/mm3) 21% and 17% had detectable HIV-1 RNA and HBV DNA, respectively. Overall 35% showed hypertension, 6% diabetes, 7% liver stiffness indicative of cirrhosis, and 18% urinary excretion of Schistosoma antigen. Tubular proteinuria occurred in 16% of patients and was independently predicted by female gender and hypertension. The eGFR declined by median 1.8 ml/min/year during TDF exposure (IQR -4.4, -0.0); more pronounced declines (≥ 5 ml/min/year) occurred in 22% of patients and were associated with receiving ritonavir-boosted lopinavir rather than efavirenz. HBV DNA, HBeAg, transaminases, and liver stiffness were not predictive of renal function abnormalities. CONCLUSIONS: The findings mandate improved diagnosis and management of hypertension and suggest targeted laboratory monitoring of patients receiving TDF alongside a booster in sub-Saharan Africa.

Prevalence and predictors of anxiety in an African sample of recent stroke survivors.

OBJECTIVES: Studies considering emotional disturbances in the setting of stroke have primarily focused on depression and been conducted in high-income countries. Anxiety in stroke survivors, which may be associated with its own unique sets of risk factors and clinical parameters, has been rarely investigated in sub-Saharan Africa (SSA). We assess the characteristics of anxiety and anxiety-depression comorbidity in a SSA sample of recent stroke survivors. MATERIALS AND METHODS: We assessed baseline data being collected as part of an intervention to improve one-year blood pressure control among recent (≤1 month) stroke survivors in SSA. Anxiety in this patient population was measured using the Hospital Anxiety and Depression Scale (HADS), while the community screening instrument for dementia was used to evaluate cognitive functioning. Independent associations were assessed using logistic regression analysis. RESULTS: Among 391 participants, clinically significant anxiety (HADS anxiety score≥11) was found in 77 (19.7%). Anxiety was comorbid with depression in 55 (14.1%). Female stroke survivors were more likely than males to have anxiety (OR=2.4, 95% CI=1.5-4.0). Anxiety was significantly associated with the presence of cognitive impairment after adjusting for age, gender and education (OR=6.8, 95% CI=2.6-18.0). CONCLUSIONS: One in five recent stroke survivors in SSA has clinically significant anxiety, and well over 70% of those with anxiety also have depression. Future studies will need to determine what specific impact post-stroke anxiety may have on post-stroke clinical processes and outcomes.

Highly Prevalent Hyperuricaemia is Associated with Adverse Clinical Outcomes Among Ghanaian Stroke Patients: An Observational Prospective Study.

BACKGROUND: Although a direct causal relationship between hyperuricaemia and stroke continues to be debated, strong associations between serum uric acid (SUA) and cerebrovascular disease exist. Very few studies have been conducted to evaluate the frequency and association between this potentially modifiable biomarker of vascular risk and stroke in sub-Saharan Africa. Therefore the aim of this study was to examine the association between hyperuricaemia and the traditional risk factors and the outcomes of stroke in Ghanaian patients. METHODS: In this prospective observational study, 147 patients presenting with stroke at a tertiary referral centre in Ghana were consecutively recruited. Patients were screened for vascular risk factors and SUA concentrations measured after an overnight fast. Associations between hyperuricaemia and stroke outcomes were analysed using Kaplan-Meier and Cox proportional hazards regression analysis. RESULTS: The frequency of hyperuricaemia among Ghanaian stroke patients was 46.3%. Non-significant associations were observed between hyperuricaemia and the traditional risk factors of stroke. SUA concentration was positively correlated with stroke severity and associated with early mortality after an acute stroke with unadjusted hazards ratio of 2.3 (1.4 - 4.2, p=0.001). A potent and independent dose-response association between increasing SUA concentration and hazard of mortality was found on Cox proportional hazards regression, aHR (95% CI) of 1.65 (1.14-2.39), p=0.009 for each 100µmol/l increase in SUA. CONCLUSIONS: Hyperuricaemia is highly frequent and associated with adverse functional outcomes among Ghanaian stroke patients. Further studies are warranted to determine whether reducing SUA levels after a stroke would be beneficial within our setting.

The profile of risk factors and in-patient outcomes of stroke in Kumasi, Ghana.

BACKGROUND: Stroke is an emerging public health challenge in Ghana requiring urgent attention for its control. Because some of the risk factors for stroke are modifiable, characterisation of these risk factors in the Ghanaian population as well as outcomes of stroke are urgently needed to guide policy for non-communicable diseases. We therefore conducted this study to evaluate the frequencies of the traditional risk factors and outcomes of stroke at the main tertiary referral centre in the middle belt of Ghana in a prospective observational study. METHODS AND RESULTS: Patients with a clinical diagnosis of stroke were consecutively recruited and vascular risk factors were assessed as well as markers of severity of stroke and in-patient treatment outcomes. 265 patients were recruited, 56.6% were females and mean ± SD age of 64.6 ± 14.54 years. 85%, 73% and 58% of patients had systemic arterial hypertension, physical inactivity and obesity respectively as common risk factors. We identified that patients with stroke had a median of 3 traditional risk factors, were unaware of the presence of these risk factors or were poorly controlled if known. Stroke was associated with a high in-patient case fatality rate of 43% principally among patients with haemorrhagic stroke. CONCLUSIONS: Our findings indicate that urgent concerted efforts are required to improve public awareness and management of the prevailing risk factors of stroke in Ghana.

Sensitivity of PCR targeting Mycobacterium ulcerans by use of fine-needle aspirates for diagnosis of Buruli ulcer.

In a previous study, we reported that the sensitivity of PCR targeting the IS2404 insertion sequence of Mycobacterium ulcerans was 98% when it was applied to 4-mm punch biopsy samples of Buruli lesions. Fine-needle aspiration (FNA) is a less traumatic sampling technique for nonulcerated lesions, and we have studied the sensitivity of PCR using FNA samples. Fine-needle aspirates were taken with a 21-gauge needle from 43 patients diagnosed clinically with M. ulcerans disease. Four-millimeter punch biopsies were obtained for microscopy, culture, and PCR targeting the IS2404 insertion sequence. The sensitivity of PCR using samples obtained by FNA was 86% (95% confidence interval [95% CI], 72 to 94%) compared with that for PCR using punch biopsy samples. In this study, the sensitivities of culture and microscopy for punch biopsy samples were 44% (95% CI, 29 to 60%) and 26% (95% CI, 14 to 41%), respectively. This demonstrates that PCR on an FNA sample is a viable minimally invasive technique to diagnose M. ulcerans lesions.

Dynamics of the cytokine response to Mycobacterium ulcerans during antibiotic treatment for M. ulcerans disease (Buruli ulcer) in humans.

We have studied the evolution of the gamma interferon (IFN-gamma) and interleukin 10 (IL-10) responses after Mycobacterium ulcerans sonicate stimulation of whole blood from patients with early M. ulcerans lesions during treatment with rifampin and streptomycin for 8 weeks. Among the 26 patients, secretion of IFN-gamma increased during treatment, with a significant increase at 4 weeks and a further increase after 8 weeks overall. The increase was more rapid in patients with large or ulcerative lesions, becoming significant by 4 weeks. For small lesions, there was only a minor increase, which did not reach significance. There was no significant change in the median IL-10 response during antibiotic therapy, and there was no inverse correlation between IFN-gamma and IL-10 responses. These results demonstrate that an IFN-gamma secretory response to M. ulcerans developed, independently of IL-10 secretion, in patients whose M. ulcerans disease healed during antibiotic therapy.