31 research outputs found
The kynurenine pathway activities in a sub-Saharan HIV/AIDS population
BACKGROUND : Tryptophan is an essential amino acid for the synthesis of proteins and important metabolites such as
serotonin, melatonin, tryptamine and niacin. After protein synthesis, more than 90 % of tryptophan catabolism
occurs along the kynurenine pathway. The inflammation-inducible enzyme indoleamine 2,3 dioxygenase (IDO) is
responsible for the first rate-limiting step in the kynurenine pathway, i.e., oxidation of tryptophan to kynurenine.
Excessive IDO activity in conditions such as HIV/AIDS may lead to tryptophan depletion and accumulation of
metabolites downstream from kynurenine. Little is known about the kynurenine pathway of HIV/AIDS patients in
sub-Saharan regions. This study, in a low income sub-Saharan HIV/AIDS population, examined the effects of
activities in the kynurenine pathway on plasma levels of tryptophan, kynurenine and the neurotoxin quinolinic acid,
and on de novo synthesis of nicotinamide.
METHODS : Plasma samples were obtained from a cohort of 105 HIV patients and 60 controls. Kynurenine pathway
metabolites were analysed using gas chromatography â mass spectrometry. ELISA and flow cytometry were used
to assess plasma inflammatory markers.
RESULTS : IDO activity, depletion of tryptophan, as well as accumulation of kynurenine and the neurotoxin quinolinic
acid, were not only significantly greater in the patients than in the controls, but also markedly greater than in
HIV/AIDS patients from developed countries. Tryptophan levels were 12.3 % higher, kynurenine levels 16.2 % lower,
quinolinic acid levels 43.2 % lower and nicotinamide levels 27,2 % lower in patients on antiretroviral treatment than
in antiretroviral-naĂŻve patients. Patientsâ kynurenine pathway metabolites correlated with the levels of inflammatory
markers, including that of the major IDO-inducer, interferon-gamma. Indications are that the rate of de novo
synthesis of nicotinamide in the kynurenine pathway correlates with increases in quinolinic acid levels up to a point
where saturation of the enzyme quinolinate phosphoribosyl transferase occurs.
CONCLUSIONS : Higher levels of inflammatory activity in this low income sub-Saharan HIV/AIDS population than in
patients from developed countries lead to greater tryptophan depletion and greater accumulation of metabolites
downstream from tryptophan with quinolinic acid levels often reaching levels associated with the development of
HIV/AIDS-associated neurocognitive dysfunction. De novo synthesis of nicotinamide from quinolinic acid contributes
to the maintenance of nicotinamide, and by implication NAD levels, in HIV/AIDS patients from low income
populations. Antiretroviral treatment partially corrects disturbances in the kynurenine pathway.Medical Research Council of South Africa and the South African Sugar Association (SASA Project 213).http://www.biomedcentral.com/bmcinfectdis/hb201
Tryptophan depletion in context of the inflammatory and general nutritional status of a low-income South African HIV-infected population
MV was the project leader. PB developed and validated the GC-MS method for
the analysis of tryptophan and performed the biochemical and immunological
analyses. MV and PB were responsible for the project design, analyses of the
results and writing of the manuscript. PL was involved in the sourcing of
patients and the clinical examination of all patients.The authors wish to thank the participants and staff of the Immunology
Clinic at Kalafong Hospital and the South African National Blood Service at
the Pretoria West satellite site.BACKGROUND : The essential amino acid tryptophan cannot be synthesised in the body and must be acquired
through dietary intake. Oxidation of tryptophan, due to immune induction of the enzyme indoleamine 2,3-
dioxygenase (IDO), is considered to be the main cause of tryptophan depletion in HIV infection and AIDS.
We examined plasma tryptophan levels in a low-income sub-Saharan HIV-infected population and compared it to
that of developed countries. Tryptophan levels were further examined in context of the general nutritional and
inflammatory status.
METHODS : This cross-sectional study included 105 HIV-positive patients recruited from the Kalafong Hospital in
Pretoria, South Africa, and 60 HIV-negative controls.
RESULTS : Patient tryptophan levels were in general markedly lower than those reported for developed countries. In
contrast to reports from developed countries that showed tryptophan levels on average to be 18.8 % lower than
their control values, tryptophan levels in our study were 44.1 % lower than our controls (24.4 ± 4.1 vs. 43.6 ±
11.9 ÎŒmol/l; p < 0.001). Tryptophan levels correlated with both CD4 counts (r = 0.341; p = 0.004) and with proinflammatory
activity as indicated by neopterin levels (r = â0.399; p = 0.0001). Nutritional indicators such as albumin
and haemoglobin correlated positively with tryptophan and negatively with the pro-inflammatory indicators
neopterin, interleukin 6 and C-reactive protein. The most probable causes of the lower tryptophan levels seen in
our population are food insecurity and higher levels of inflammatory activity.
CONCLUSIONS : We contend that inflammation-induced tryptophan depletion forms part of a much wider effect of
pro-inflammatory activity on the nutritional profile of HIV-infected patients.This research was supported by grant funding
received from the Medical Research Council of South Africa and the South
African Sugar Association (SASA Project 213).http://www.jhpn.net/index.php/jhpnam2016Internal MedicinePhysiologyPsychiatr
Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa
Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the
Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector âactive patientsâ (â„1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19
cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using
modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with
COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70â2.70), with similar risks across strata of
viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR,
2.70 [95% CI, 1.81â4.04] and 1.51 [95% CI, 1.18â1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39
(95% CI, 1.96â2.86); population attributable fraction 8.5% (95% CI, 6.1â11.1)
Retention of medical officers in the district health services of the Western Cape, South Africa: An exploratory descriptive qualitative study
Background:Â An adequate health workforce is an essential building block of effective health systems. In South Africa, medical officers (MOs) are a key component of service delivery in district health services. The Stellenbosch University Family Physician Research Network in the Western Cape identified that retention of MOs was a key issue. The aim of this study was to explore the factors that influence the retention of MOs in public sector district health services in the Western Cape, South Africa.Methods:Â This is a descriptive exploratory qualitative study. Medical officers were purposefully selected in terms of districts, facility types, gender, seniority and perceived likelihood of leaving in the next four years. Semi-structured interviews were performed by family physicians, and the qualitative data were analysed using the framework method.Results:Â Fourteen MOs were interviewed, and four major themes were identified: career intentions; experience of clinical work; experience of the organisation; and personal, family and community issues. Key issues that influenced retention were: ensure that the foundational elements are in place (e.g. adequate salary and good infrastructure), nurture cohesive team dynamics and relationships, have a family physician, continue the shift towards more collaborative and appreciative management styles, create stronger career pathways and opportunities for professional development in the district health services, be open to flexible working hours and overtime, and ensure workload is manageable.Conclusion:Â A number of important factors influencing retention were identified. Leaders and managers of the healthcare services could intervene across these multiple factors to enhance the conditions needed to retain MOs