Neurological disorders in Northern Tanzania: A 6-year prospective hospital-based case series

Background: The burden of neurological disorders is large and altered by the HIV epidemic. Objectives: We describe the pattern of neurological disorders and their association with HIV infection in adult patients attending a consultant hospital in Northern Tanzania. Methods: In this prospective cross-sectional study, we collected data on adult neurological referrals over a 6-year period between 2007-13. The odds of HIV infection, across neurological categories adjusted for age and sex, was calculated. Results: Of 2037 participants, 54.8% were male and 45.2% were female. The median age of participants was 43 years. The results for HIV screening were available for 992/2037 (48.7%) patients, of whom 306 (30.8%) were seropositive. The most frequent neurological disorders were cerebrovascular disease (19.9%), paraplegia (13.6%), and peripheral neuropathies (8%). Taken together CNS infection accounted for 278/2037 (13.6%). The adjusted odds (aOR) of HIV infection was highest amongst infections; brain abscesses (aOR 107, 95% CI 35.1-470.4) and meningitis/encephalitis (aOR 40.1, 95% CI 13.6-172.9), but also raised in cerebrovascular disease, paraplegia, peripheral neuropathies, cranial nerve palsies, seizures, cerebllar disorders, movement disorders, motor neuron disease and headache. Conclusion: The main pattern of neurological disorders in Northern Tanzania is presented. The odds of HIV infection was highest in CNS infections and in a wide range of non-communicable neurological disorders.publishedVersio

The burden of multimorbidity-associated acute hospital admissions in Malawi and Tanzania:a prospective multicentre cohort study

Background: The global burden of multimorbidity—the coexistence of two or more long-term conditions—is increasing. Limited access to primary care in sub-Saharan Africa means acute hospital admission is often the sentinel multimorbidity presentation. This prospective multicentre cohort study aimed to describe the burden, constituent diseases, and outcomes of multimorbidity among patients acutely admitted to hospital in Malawi and Tanzania. Methods: Adults (ie, those aged ≥18 years) admitted to four hospitals (two tertiary and two district hospitals) with acute medical conditions were consecutively recruited within 24 h of presentation and followed up for 90 days. We estimated the prevalence of HIV infection, diabetes, hypertension, and chronic kidney disease using commercially available point-of-care tests, and captured self-reported and clinical diagnoses (n/N [%]). Health economic data were summarised by median and IQR and modelled using generalised linear models. All-cause 90-day mortality was summarised with Kalplan–Meier plots and analysed using Cox regression models. Findings: 1407 adults (657 [46·7%] were female and 750 [53·3%] were male; mean age was 52·3 years [SD 18·4]) were recruited. We examined multimorbidity prevalence in 1007 participants admitted to three hospitals that accept admissions directly from the community. Multimorbidity was found in 473 (47·0%) of 1007 participants and 292 (29·0%) had a single long-term condition. Outcomes at 90 days were determined for 1317 (93·6%) of 1407 participants. Adjusted 90-day mortality was higher in participants with multimorbidity (335 [41·7%] of 804; hazard ratio 1·5 [95% CI 1·1–2·1]) and those with one long-term condition (80 [28·3%] of 283; 1·5 [1·0–2·1]); compared with those with no long-term conditions (31 [13·5%] of 230). Health-related quality of life was lower in participants with multimorbidity compared with those with one long-term condition (median 0·402 [IQR –0·037 to 0·644] vs 0·557 [0·140 to 0·730]; p=0·005) at baseline, and at final observation (0·858 [0·667 to 1·00] vs 1·00 [0·589 to 1·00] respectively; p=0·01). In Tanzania, medical costs incurred by patients were higher in participants with multimorbidity compared with those with one long-term condition (relative effect 5·77 [95% CI 2·99–11·15]; p&lt;0·0001). Interpretation: Multimorbidity is common in patients admitted to hospital in Malawi and Tanzania and associated with worse survival and increased cost. Multimorbidity is an urgent public health threat that requires fundamental health-care delivery reform to address population needs. Funding: National Institute for Health and Care Research and Wellcome Trust. Translations: For the Chichewa and Kiswahili translations of the abstract see Supplementary Materials section.</p

Multimorbidity-associated emergency hospital admissions: a “screen and link” strategy to improve outcomes for high-risk patients in sub-Saharan Africa: a prospective multicentre cohort study protocol

Background The prevalence of multimorbidity (the presence of two or more chronic health conditions) is rapidly increasing in sub–Saharan Africa. Hospital care pathways that focus on single presenting complaints do not address this pressing problem. This has the potential to precipitate frequent hospital readmissions, increase health system and out-of-pocket expenses, and may lead to premature disability and death. We aim to present a description of inpatient multimorbidity in a multicentre prospective cohort study in Malawi and Tanzania. Primary objectives Clinical: Determine prevalence of multimorbid disease among adult medical admissions and measure patient outcomes. Health Economic: Measure economic costs incurred and changes in health-related quality of life (HRQoL) at 90 days post-admission. Situation analysis: Qualitatively describe pathways of patients with multimorbidity through the health system. Secondary objectives Clinical: Determine hospital readmission free survival and markers of disease control 90 days after admission. Health Economic: Present economic costs from patient and health system perspective, sub-analyse costs and HRQoL according to presence of different diseases. Situation analysis: Understand health literacy related to their own diseases and experience of care for patients with multimorbidity and their caregivers. Methods This is a prospective longitudinal cohort study of adult (≥18 years) acute medical hospital admissions with nested health economic and situation analysis in four hospitals: 1) Queen Elizabeth Central Hospital, Blantyre, Malawi; 2) Chiradzulu District Hospital, Malawi; 3) Hai District Hospital, Boma Ng’ombe, Tanzania; 4) Muhimbili National Hospital, Dar-es-Salaam, Tanzania. Follow-up duration will be 90 days from hospital admission. We will use consecutive recruitment within 24 hours of emergency presentation and stratified recruitment across four sites. We will use point-of-care tests to refine estimates of disease pathology. We will conduct qualitative interviews with patients, caregivers, healthcare providers and policymakers; focus group discussions with patients and caregivers, and observations of hospital care pathways

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches