Tenofovir alafenamide: An initial experience at Groote Schuur Hospital, Cape Town, South Africa.

BACKGROUND: Hepatitis B virus (HBV) remains endemic in South Africa (SA), with a concomitantly high prevalence of HIV co-infection. Chronic kidney disease in these subpopulations also has a high prevalence. Tenofovir is an important component of management, but the associated risk of nephrotoxicity makes dosing a challenge in patients with impaired kidney function. A new formulation, tenofovir alafenamide fumarate (TAF), with a more favourable renal toxicity profile, is now available. OBJECTIVES: To evaluate our initial experience of TAF use at Groote Schuur Hospital, Cape Town. METHODS: We retrospectively reviewed patients with HBV mono-infection and HIV-HBV co-infection who were initiated on TAF since 2018. We recorded all relevant demographic, serological, virological and biochemical data from patient records. Adherence was documented by pill collection at the pharmacy. RESULTS: A total of 26 patients were included in the evaluation, median (interquartile range (IQR)) age 48 (39 - 51) years, 73% (n=19) male, 27% (n=7) hepatitis B e-antigen-positive, and 46% (n=12) HIV co-infected. The median (IQR) duration of treatment with TAF was 13 (9 - 15) months. The median (IQR) baseline creatinine level was 180 (130 - 227) µmol/L, with significant improvement at 12 months, 122 (94 - 143) µmol/L; p=0.017. Reflecting this change, the estimated glomerular filtration rate improved significantly from baseline to month 12 (42 (25 - 52) and 51 (48 - 68) mL/min/1.73 m2, respectively; p=0.023). Similarly, serum alanine aminotransferase (ALT) normalised from a baseline of 33 (18 - 52) to 18 (15 - 24) U/L at month 12 (p=0.012). HBV DNA viral load also declined, from a baseline of log10 4.04 (2.5 - 7.8) IU/mL to a median of <log10 1.3 IU/mL at month 12. HIV viral load was less than the lower level of quantification at months 6 and 12. CONCLUSIONS: TAF was well tolerated, with stable and significantly improving kidney function throughout a 12-month follow-up period. Serum ALT normalised, mirrored by declining HBV viral load. HIV viral load remained undetectable at 6 and 12 months.

Sustained reduction in antibiotic consumption in a South African public sector hospital; Four year outcomes from the Groote Schuur Hospital antibiotic stewardship program.

BACKGROUND: Overuse of antibiotics has driven global bacterial resistance to the extent that we have entered a post-antibiotic era, where infections that were once easily treatable are now becoming untreatable. Efforts to control consumption have focused on antibiotic stewardship programmes (ASPs), aimed at optimising use. OBJECTIVE: To report antibiotic consumption and cost over 4 years from a public hospital ASP in South Africa (SA). METHODS: A comprehensive ASP comprising online education, a dedicated antibiotic prescription chart and weekly dedicated ward rounds was introduced at Groote Schuur Hospital, Cape Town, in 2012. Electronic records were used to collect data on volume and cost of antibiotics and related laboratory tests, and to determine inpatient mortality and 30-day readmission rates. These data were compared with a control period before the intervention. RESULTS: Total antibiotic consumption fell from 1 046 defined daily doses/1 000 patient days in 2011 (control period) to 868 by 2013 and remained at similar levels for the next 2 years. This was driven by reductions in intravenous antibiotic use, particularly ceftriaxone. Inflation-adjusted cost savings on antibiotics were ZAR3.2 million over 4 years. Laboratory tests increased over the same period with a total increased cost of ZAR0.4 million. There was no significant change in mortality or 30-day readmission rates. CONCLUSIONS: The effects of a comprehensive ASP on medical inpatients at a public sector hospital in SA were durable over 4 years, leading to a reduction in total antibiotic consumption without adverse effect. When increased laboratory costs were offset there was a net cost saving of ZAR2.8 million.

Hematological recovery in male ultramarathon runners: the effect of variations in training load and running time.

AIM: Haematological response to the 2001 downhill Comrades Marathon was compared in high (>120 km/w in training; 3 weeks of pre-race taper) and low (<80 km/w in training; 2 weeks of pre-race taper) training status groups. METHODS: Full blood counts, differential lymphocyte counts (CD3, CD4, CD8, CD19, CD56), serum cortisol, C-reactive protein (CRP) and creatine kinase (CK) were measured in blood samples donated 21 hours before and 16 hours after a 90 km ultramarathon. RESULTS: Despite significantly faster mean race finishing time (8.03 h vs 10.53 h; p<0.001) and greater percentage incidence (55.6% vs 40%) of post-race upper respiratory tract infection (URTI) in the highly trained group, these faster runners did not show evidence of a slower post-race recovery in terms of total leukocyte, neutrophil, total or differential lymphocyte counts (p>0.05). CRP concentrations were, however, markedly higher in the slower, less trained group (65.3+/-10.7 vs 38.3+/-5.9; p<0.01). CONCLUSIONS: Despite greater systemic evidence of post-race muscle inflammation and an acute phase response in the slower runners in a downhill ultramarathon race, the haematological recovery of well trained runners who undergo a 3-week taper period prior to the ultramarathon is not different to that in less trained runners who spend almost 3 hours longer on the road. The higher prevalence of post-race URTI symptoms in the fast, well trained group does not appear to be related to lymphocyte recovery in peripheral blood.

Mycotoxins in South African traditionally brewed beers.

Traditionally brewed alcoholic beverages are regularly consumed by most ethnic black South Africans. Maize and barley, both of which are used for producing locally brewed alcoholic beer, are frequently contaminated by mycotoxin-producing moulds. The study was undertaken to investigate whether these toxins are present in raw grains and the traditional beers imbibed by the local black African population. It was established that the raw ingredients (sorghum, sorghum malt grains, maize grits), commercially produced traditional beers (Utshwala and Utshwala special) and home-brewed beers (Umqombotha, Isiqatha, Imfulamfula) were contaminated by bacteria and fungi (both yeasts and moulds). The contaminating moulds were isolated and identified. The contaminated samples were analysed for aflatoxins B1, B2, G1 and G2, zearalenone, citrinin, deoxynivalenol, and ochratoxin A using a multi-mycotoxin thin-layer chromatography screening method and the toxins were quantified by high-performance liquid chromatography. Grain samples were infected by. Aspergillus flavus, A. alliaceus, A. clavatus, Penicillium spp., Rhizopus spp. and Mucor spp. Sorghum malt grain samples contained the toxin zear alenone. No mycotoxin-producing fungi were present in the fermented beers but two of six commercial beer samples contained aflatoxins (200 and 400 microg l(-1) and 45% (13 of 29) of the home-brewed beers had zear alenone (range 2.6-426 microg l(-1) and/or ochratoxin A (3-2340 microg l(-1).

The increasing burden of tuberculosis in pregnant women, newborns and infants under 6 months of age in Durban, KwaZulu-Natal.

OBJECTIVES: In spite of the global epidemic of tuberculosis (TB) which has been exacerbated by HIV, the impact of these co-infections on maternal and perinatal health has been limited. We document new evidence from Durban, KwaZulu-Natal, on the increasing effects of TB in pregnant women, neonates and infants. METHOD: Women with TB were prospectively studied at the antenatal clinics and obstetric and labour wards at King Edward VIII Hospital, Durban, between 1996 and 1998. The incidence of TB was calculated, and the population-attributable fraction of TB due to HIV infection in pregnancy was estimated. Concurrently, culture-confirmed cases of Mycobacterium tuberculosis in neonates and infants under 6 months of age at the hospital were documented. RESULTS: One hundred and forty-six cases of maternal TB were detected. TB occurred in 0.1% and 0.6% of maternities in 1996 and 1998 respectively. Overall, TB rates for HIV non-infected maternities was 72.9/10(5), and for HIV-infected maternities, 774.5/10(5). The attributable fraction of TB related to HIV in pregnancy was 71.7%; 10.3% of these mothers died. There was a 2.2-fold increase in the caseload of culture-confirmed TB in neonates and young infants at the hospital. CONCLUSION: In regions where TB and HIV prevalence is high, efforts to improve maternal and perinatal health must include the detection of TB in pregnancy.

Correlation of CD4:CD8 ratio and tumour necrosis factor (TNF)alpha levels in induced sputum with bronchoalveolar lavage fluid in pulmonary sarcoidosis.

BACKGROUND: An increased CD4:CD8 lymphocyte ratio and raised cytokine levels in bronchoalveolar lavage (BAL) fluid are characteristic of pulmonary sarcoidosis. Sputum induction has been used as a non-invasive tool for investigating the airways and may be useful in investigating inflammation in patients with sarcoidosis in whom endobronchial, peribronchial, and parenchymal inflammation is present. This study aimed to correlate the total and differential cell counts, CD4:CD8 ratio, and tumour necrosis factor (TNF)alpha levels between induced sputum and BAL fluid in patients with pulmonary sarcoidosis. METHODS: Fourteen patients with newly diagnosed biopsy proven sarcoidosis and six healthy controls were investigated. Sputum induction and BAL was carried out at the initial visit and repeated following six months of treatment with oral prednisone. RESULTS: There was no correlation of differential cell counts between induced sputum and BAL fluid. The CD4:CD8 ratio in induced sputum correlated strongly with that in BAL fluid (5.5 (0. 4:1) versus 4.4 (0.2:1); r = 0.8, p<0.001) and the fall in the ratio following six months of treatment in sputum paralleled that in BAL fluid (3.4 (0.2:1) versus 2.4 (0.2:1)). The TNF alpha levels in sputum also correlated with levels in the BAL fluid (11.9 (1.5) pg/ml versus 17.6 (2.7) pg/ml; r = 0.8, p<0.001). The fall in sputum TNF alpha levels following six months of treatment paralleled the fall in BAL fluid levels (6.7 (0.9) pg/ml versus 11.6 (1.3) pg/ml). CONCLUSIONS: The CD4:CD8 ratio and TNF alpha levels in induced sputum correlated with those in BAL fluid and paralleled changes with treatment. Induced sputum may therefore be a non-invasive surrogate for certain parameters in BAL fluid in patients with sarcoidosis.

Cytokine expression in patients with treated congenital hydrocephalus: a preliminary report of five patients.

BACKGROUND: Previous studies have described the elaboration of cytokines in experimental models of congenital hydrocephalus using rats or mice. However, there have been no reports of similar studies in humans. OBJECTIVE: To determine the cytokine expression pattern in the cerebrospinal fluid (CSF) of patients with treated congenital hydrocephalus. DESIGN: A prospective study. SETTING: Wentworth Hospital, Durban, South Africa. SUBJECTS: Five patients (three infants and two older patients) with congenital hydrocephalus treated by means of a ventriculoperitoneal shunt. INTERVENTIONS: Immunophenotyping of peripheral blood was performed on a flow cytometer. The isolation, in-vitro stimulation of peripheral blood and CSF mononuclear cells, and intracellular cytokine determination by flow cytometry were performed. MAIN OUTCOME MEASURES: Peripheral blood and CSF cytokine measurements. RESULTS: Although not statistically significant, all measured mean cytokine levels in the peripheral blood of the infant group were consistently higher than that of the adult group. CSF cytokine levels in both groups were similar and unremarkable. CONCLUSION: No clear pattern of CSF cytokine elaboration, either type-1 (T helper 1) (Th1) or Type-2 (T helper 2) (Th2), could be demonstrated in either of the groups. The significance of higher peripheral blood cytokine levels in the infants is unclear, but may be age-related, and is not apparent in the CSF.

High intensity exercise: a cause of lymphocyte apoptosis?

Post exercise lymphocytopenia is well documented and attributed to egress of lymphocytes from the vascular compartment. Recent studies have reported exercise induced DNA damage in leukocytes and have questioned a possible link to apoptosis. Eleven subjects underwent a ramped treadmill test to exhaustion. Venous blood samples were taken before, immediately post exercise, and 24 and 48 hours after exercise. Single cell gel electrophoresis revealed evidence of single strand DNA damage in 10% of lymphocytes immediately after exercise, but not at other times. Fluorescent microscopy showed three patterns of DNA distribution, similar to those seen in apoptosis, at all times after exercise. Three subjects underwent the same exercise protocol, and lymphocytes were prepared for flow cytometry to determine apoptosis using the TUNEL method. Flow cytometry revealed lymphocyte apoptosis in 63% of lymphocytes immediately after exercise and 86.2%, 24 hours after exercise. Lymphocyte apoptosis is documented for the first time after exercise and may in part account for exercise induced lymphocytopenia and reduced immunity.