Peritoneal dialysis technique survival at Tygerberg Hospital in Cape Town, South Africa

Background: The use of peritoneal dialysis (PD) as a treatment modality for patients with end-stage renal disease (ESRD) has been declining in many countries over the past few years. One of the reasons is technique failure, which occurs more frequently than is the case with chronic haemodialysis. Identifying and addressing the causes of technique failure is important in order to maintain more patients on PD, especially in settings where there are limited resources for chronic haemodialysis and a “PD first” approach is followed.Methods: In this retrospective study at Tygerberg Hospital in Cape Town, South Africa, we investigated 170 patients who were started on chronic ambulatory PD between January 2008 and July 2014, and determined rates of technique and patient survival. Demographic, clinical and laboratory data were assessed to identify risk factors for these outcomes.Results: The median age of the patients was 36 years and the most common cause of ESRD was glomerulonephritis. Only one patient had diabetes mellitus. Technique survival at 1, 3 and 5 years was 80%, 54% and 39%, respectively, while patient survival was 90%, 82% and 63%. Patients started on PD during the second half of the study period had improved rates of technique survival. Peritonitis was the most common cause of technique failure. Increasing age and Black ethnicity were associated with increased likelihood of technique failure. Other clinical and social factors were not significantly associated with the occurrence of technique failure.Conclusions: In our patients on PD, peritonitis, increased age and Black ethnicity were important factors associated with the development of technique failure. Concerted efforts are required to reduce peritonitis rates at our centre as this is the leading cause of technique failure

Damaged Intestinal Epithelial Integrity Linked to Microbial Translocation in Pathogenic Simian Immunodeficiency Virus Infections

The chronic phase of HIV infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or CD4+ T cell count. Recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically HIV-infected humans or SIV-infected Asian macaques. We analyzed tissues from SIV-infected rhesus macaques (RMs) to provide direct in situ evidence for translocation of microbial constituents from the lumen of the intestine into the lamina propria and to draining and peripheral lymph nodes and liver, accompanied by local immune responses in affected tissues. In chronically SIV-infected RMs this translocation is associated with breakdown of the integrity of the epithelial barrier of the gastrointestinal (GI) tract and apparent inability of lamina propria macrophages to effectively phagocytose translocated microbial constituents. By contrast, in the chronic phase of SIV infection in sooty mangabeys, we found no evidence of epithelial barrier breakdown, no increased microbial translocation and no pathological immune activation. Because immune activation is characteristic of the chronic phase of progressive HIV/SIV infections, these findings suggest that increased microbial translocation from the GI tract, in excess of capacity to clear the translocated microbial constituents, helps drive pathological immune activation. Novel therapeutic approaches to inhibit microbial translocation and/or attenuate chronic immune activation in HIV-infected individuals may complement treatments aimed at direct suppression of viral replication

CD14+ macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide

BACKGROUND : Intestinal macrophages are key regulators of inflammatory responses to the gut microbiome and play a central role in maintaining tissue homeostasis and epithelial integrity. However, little is known about the role of these cells in HIV infection, a disease fuelled by intestinal inflammation, a loss of epithelial barrier function and increased microbial translocation (MT). METHODS : Phenotypic and functional characterization of intestinal macrophages was performed for 23 African AIDS patients with chronic diarrhea and/or weight loss and 11 HIV-negative Africans with and without inflammatory bowel disease (IBD). AIDS patients were treated with cotrimoxazole for the prevention of opportunistic infections (OIs). Macrophage phenotype was assessed by flow cytometry and immuno-histochemistry (IHC); production of proinflammatory mediators by IHC and Qiagen PCR Arrays; in vitro secretion of cytokines by the Bio-Plex Suspension Array System. Statistical analyses were performed using Spearman’s correlation and Wilcoxon matched-pair tests. Results between groups were analyzed using the Kruskal-Wallis with Dunn’s post-test and the Mann–Whitney U tests. RESULTS : None of the study participants had evidence of enteric co-infections as assessed by stool analysis and histology. Compared to healthy HIV-negative controls, the colon of AIDS patients was highly inflamed with increased infiltration of inflammatory cells and increased mRNA expression of proinflammatory cytokine (tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IFN-γ, and IL-18), chemokines (chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C) motif ligand (CXCL)10) and transcription factors (TNF receptor-associated factor (TRAF)6 and T-box (TXB)21). IHC revealed significant co-localization of TNF-α and IL-1β with CD68+ cells. As in IBD, HIV was associated with a marked increase in macrophages expressing innate response receptors including CD14, the co-receptor for lipopolysaccharide (LPS). The frequency of CD14+ macrophages correlated positively with plasma LPS, a marker of MT. Total unfractionated mucosal mononuclear cells (MMC) isolated from the colon of AIDS patients, but not MMC depleted of CD14+ cells, secreted increased levels of proinflammatory cytokines ex vivo in response to LPS CONCLUSIONS : Intestinal macrophages, in the absence of overt OIs, play an important role in driving persistentinflammation in HIV patients with late-stage disease and diarrhea. These results suggest intensified treatmentstrategies that target inflammatory processes in intestinal macrophages may be highly beneficial in restoringthe epithelial barrier and limiting MT in HIV-infected patients.This research and selected researchers (EC, TR, PM, SM and CS) were funded in part by a grant from the Delegation of the European Union to South Africa: “Drug Resistance Surveillance and Treatment Monitoring Network for the Public Sector HIV Antiretroviral Treatment Programme in the Free State – Sante 2007/147-790” and by a grant from the National Research Council of South Africa, Unlocking the Future 61509.http://www.biomedcentral.com/bmcinfectdisam201

Performance of modified WHO presumptive criteria for diagnosis of HIV infection in children

Background: Making a diagnosis of HIV infection in children aged less than 18 months remains a challenge in low resource settings like Zambia due to the limited availability of gold standard testing with HIV DNA PCR. Clinicians in rural areas have to depend on clinical diagnosis to start HAART asthey wait for the dry blood spot (DBS) for DNAPCR results sent from the urban centers.Methods: This descriptive cross-sectional study was performed at the University Teaching Hospital, Lusaka, Zambia. 299 HIV-exposed children aged less than 18 months were enrolled following a consent procedure. Patients were evaluated for HIV infection based on the World Health Organization's presumptive diagnostic criteria (WHO-PDC), integrated management of childhood illnesses (IMCI) criteria, select physical exam abnormalities, and CD4% and findings were compared with HIVDNAPCR results.Results: Of the 299 exposed patients analyzed, 111(37%) were found to be HIV-positive by DNA PCR. The median CD4% in the infected children was 18%. WHO-PDC used on its own had 23% sensitivity (95% CI 17-32%) and 93% specificity (88-96%), respectively, whereas IMCI criterion had 10% sensitivity (6-17%) and 97% specificity (94-99%), respectively.  Multivariate analysis was used to identify the most sensitive predictors when combined with the WHO-PDC and IMCI criterion. WHO-PDC with CD4% improved the sensitivity to 77% (68-83%) with a specificity of 83% (77-88%), positive predictive value (PPV) of 73% (64-80%) and negative predictive value (NPV) of 86% (80-90%). IMCI with CD4% improved sensitivity to 80% (71-87%) with a specificity of 88% (82-92%), PPV 78% (69-85%) and NPV 89% (84-93%). The addition of individual physical exam findings without CD4% improved the sensitivity of WHOPDC only modestly. When the WHO-PDC, weight<3rd percentile, hepatomegaly, splenomegaly, lymphadenopathy and CD4% were combined, the sensitivity improved to 85% (77-90%), specificity 63% (56-70%), PPV 58% (50-65%) and NPV of 88% (81-92%).Conclusion: The WHO-PDC clinical algorithm can be improved when combined with a CD4% <25% in children less than 12 months of age and CD4% <20% in those between 12 and 18 months.Keywords: HIV, early infant diagnosis, diagnosis, Zambi

Peritoneal dialysis technique survival at Tygerberg Hospital in Cape Town, South Africa

CITATION: Kapembwa, K., et al. 2017. Peritoneal dialysis technique survival at Tygerberg Hospital in Cape Town, South Africa. African Journal of Nephrology, 20(1):25-33, doi:10.21807/20-1-1917.The original publication is available at http://www.journals.ac.za/index.php/ajn/Background: The use of peritoneal dialysis (PD) as a treatment modality for patients with end-stage renal disease (ESRD) has been declining in many countries over the past few years. One of the reasons is technique failure, which occurs more frequently than is the case with chronic haemodialysis. Identifying and addressing the causes of technique failure is important in order to maintain more patients on PD, especially in settings where there are limited resources for chronic haemodialysis and a “PD first” approach is followed. Methods: In this retrospective study at Tygerberg Hospital in Cape Town, South Africa, we investigated 170 patients who were started on chronic ambulatory PD between January 2008 and July 2014, and determined rates of technique and patient survival. Demographic, clinical and laboratory data were assessed to identify risk factors for these outcomes. Results: The median age of the patients was 36 years and the most common cause of ESRD was glomerulonephritis. Only one patient had diabetes mellitus. Technique survival at 1, 3 and 5 years was 80%, 54% and 39%, respectively, while patient survival was 90%, 82% and 63%. Patients started on PD during the second half of the study period had improved rates of technique survival. Peritonitis was the most common cause of technique failure. Increasing age and Black ethnicity were associated with increased likelihood of technique failure. Other clinical and social factors were not significantly associated with the occurrence of technique failure. Conclusions: In our patients on PD, peritonitis, increased age and Black ethnicity were important factors associated with the development of technique failure. Concerted efforts are required to reduce peritonitis rates at our centre as this is the leading cause of technique failure.http://www.journals.ac.za/index.php/ajn/article/view/1917Publisher's versio

Quality of life in patients on chronic dialysis in South Africa : a comparative mixed methods study

CITATION: Tannor, E. K., et al. 2017. Quality of life in patients on chronic dialysis in South Africa : a comparative mixed methods study. BMC Nephrology, 18:4, doi:10.1186/s12882-016-0425-1.The original publication is available at http://bmcnephrol.biomedcentral.comBackground: The increasing prevalence of treated end-stage renal disease and low transplant rates in Africa leads to longer durations on dialysis. Dialysis should not only be aimed at prolonging lives but also improve quality of life (QOL). Using mixed methods, we investigated the QOL of patients on chronic haemodialysis (HD) and peritoneal dialysis (PD). Methods: We conducted a cross-sectional study at Tygerberg Hospital in Cape Town, South Africa. All the PD patients were being treated with continuous ambulatory peritoneal dialysis. The KDQOL-SF 1.3 questionnaire was used for the quantitative phase of the study. Thereafter, focus-group interviews were conducted by an experienced facilitator in groups of HD and PD patients. Electronic recordings were transcribed verbatim and analysed manually to identify emerging themes. Results: A total of 106 patients completed questionnaires and 36 of them participated in the focus group interviews. There was no difference between PD and HD patients in the overall KDQOL-SF scores. PD patients scored lower with regard to symptoms (P = 0.005), energy/fatigue (P = 0.025) and sleep (P = 0.023) but scored higher for work status (P = 0.005) and dialysis staff encouragement (P = 0.019) than those on HD. Symptoms and complications were verbalised more in the PD patients, with fear of peritonitis keeping some housebound. PD patients were more limited by their treatment modality which impacted on body image, sexual function and social interaction but there were less dietary and occupational limitations. Patients on each modality acknowledged the support received from family and dialysis staff but highlighted the lack of support from government. PD patients had little opportunity for interaction with one another and therefore enjoyed less support from fellow patients. Conclusions: PD patients experienced a heavier symptom burden and greater limitations related to their dialysis modality, especially with regards to social functioning. The mixed-methods approach helped to identify several issues affecting quality of life which are amenable to intervention.http://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-016-0425-1Publisher's versio

Planned early delivery versus expectant management to reduce adverse pregnancy outcomes in pre-eclampsia in a low- and middle-income setting: study protocol for a randomised controlled trial (CRADLE-4 Trial)

BACKGROUND: Pre-eclampsia is a pregnancy complication characterised by high blood pressure and multi-organ dysfunction in the mother. It is a leading contributor to maternal and perinatal mortality, with 99% of these deaths occurring in low- and middle-income countries (LMIC). Whilst clear guidelines exist for management of early-onset (< 34 weeks) and term (≥ 37 weeks) disease, the optimal timing of delivery in pre-eclampsia between 34+ 0 and 36+ 6 weeks is less clear. In a high-income setting, delivery may improve maternal outcomes without detriment to the baby, but this intervention is yet to be evaluated in LMIC. METHODS: The CRADLE-4 Trial is a non-masked, randomised controlled trial comparing planned early delivery (initiation of delivery within 48 h of randomisation) with routine care (expectant management) in women with pre-eclampsia between 34+ 0 and 36+ 6 weeks' gestation in India and Zambia. The primary objective is to establish whether a policy of planned early delivery can reduce adverse maternal outcomes, without increasing severe neonatal morbidity. DISCUSSION: The World Health Organization recommends delivery for all women with pre-eclampsia from 37 weeks onwards, based on evidence showing clear maternal benefit without increased neonatal risk. Before 34 weeks, watchful waiting is preferred, with delivery recommended only when there is severe maternal or fetal compromise, due to the neonatal risks associated with early preterm delivery. Currently, there is a lack of guidance for clinicians managing women with pre-eclampsia between 34+ 0 and 36+ 6 weeks. Early delivery benefits the mother but may increase the need for neonatal unit admission in the infant (albeit without serious morbidity at this gestation). On the other hand, waiting to deliver may increase the risk of stillbirth, fetal growth restriction and hypoxic brain injury in the neonate as a result of severe maternal complications. This is especially true for LMIC where there is a higher prevalence of adverse events. The balance of risks and benefits therefore needs to be carefully assessed before making firm recommendations. This is the first trial evaluating the optimal timing of delivery in pre-eclampsia in LMIC, where resources and disease burden are considerably different. TRIAL REGISTRATION: ISRCTN 10672137 . Registered on 28 November 2019