Prevalence and seasonality of common viral respiratory pathogens, including Cytomegalovirus in children, between 0-5 years of age in KwaZulu-Natal, an HIV endemic province in South Africa.

BACKGROUND: Acute respiratory tract infections contribute significantly to morbidity and mortality among young children in resource-poor countries. However, studies on the viral aetiology of acute respiratory infections, seasonality and the relative contributions of comorbidities such as immune deficiency states to viral respiratory tract infections in children in these countries are limited. METHODS: A retrospective analysis of laboratory test results of upper or lower respiratory specimens of children between 0 and 5 years of age collected between 1st January 2011 and 31st July 2015 from hospitals in KwaZulu-Natal, South Africa. Respiratory specimens were tested for viral respiratory pathogens using multiplex polymerase chain reaction (PCR), HIV testing was performed either by serological or PCR methods. Cytomegalovirus (CMV) respiratory infection was determined using the CMV R-gene PCR kit. RESULTS: In total 2172 specimens were analysed, of which 1175 (54.1%) were from males. The median age was 3.0 months (interquartile range [IQR] 1-7). Samples from the lower respiratory tract accounted for 1949 (89.7%) of all specimens. Respiratory multiplex PCR results were positive in 834 (45.7%) specimens. Respiratory syncytial virus (RSV) was the most commonly detected virus in 316 (32.1%) patients, followed by adenovirus (ADV) in 215 (21.8%), human rhinovirus (Hrhino) in 152 (15.4%) and influenza A (FluA) in 50 (5.1%). A seasonal time series pattern was observed for ADV (winter peak), enterovirus (EV) (autumn), human bocavirus (HBoV) (summer), and parainfluenza viruses 1 and 3 (PIV1 and 3) (spring). Stationary or untrended seasonal variation was observed for FluA (winter peak) and RSV (summer). HIV results were available for 1475 (67.9%) specimens; of these 348 (23.6%) were positive. CMV results were available for 714 (32.9%) specimens, of which 416 (58.3%) were positive. There was a statistically significant association between the coinfection of HIV and CMV with ADV. CONCLUSIONS: In this study, we identified the most common respiratory viral pathogens detected among hospitalized children in KwaZulu-Natal. The coinfection between HIV and CMV was found to be associated with an increased risk of only adenovirus infection. Most viral pathogens showed a seasonal trend of occurrence. Our data has implications for the rational design of public health programmes.

Detection of human immunodeficiency virus-1 ribonucleic acid in the peritoneal effluent of renal failure patients on highly active antiretroviral therapy.

Background: We evaluated the shedding of human immunodeficiency virus (HIV)-1 particles into continuous ambulatory peritoneal dialysis (CAPD) effluents of HIV-positive patients with end-stage renal disease (ESRD). Methods: A total of 58 HIV-positive patients with ESRD on highly active antiretroviral therapy (HAART) who had Tenckhoff catheters inserted between September 2012 and February 2015 were prospectively reviewed and followed for 18 months. Peritoneal dialysis (PD) effluent samples from functioning CAPD catheters and plasma samples were obtained at three points during regular clinic visits on days 45 ± 37, 200 ± 19 and 377 ± 13 after catheter insertion. All specimens were stored at -20°C, and each batch was analysed by Roche quantitative HIV-1 polymerase chain reaction assay to detect HIV-1 particles. Clustered logistic regression was used to test for independent predictors of HIV-1 detection in CAPD effluents. Results: HIV-1 RNA above 20 copies/mL assay limit was detectable in 19% (first batch), 26.3% (second batch) and 20% (third batch) of PD effluent specimens. HIV-1 RNA was detectable in PD fluid, without corresponding detection in the paired plasma in 3.4% (first batch), 5.3% (second batch) and 10% (third batch) of samples. Detection of HIV-1 in plasma sample (odds ratios 3.94; 95% confidence interval 1.14-13.55; P = 0.030), body mass index, serum albumin and HAART regimen were found to be significantly associated with HIV-1 detection in PD effluents. Conclusions: HIV particles are shed in detectable amounts into CAPD effluents even in patients with suppressed plasma viral load, raising concerns of a localized sanctuary site and potential infectivity of HIV-positive CAPD patients on a full complement of HAART.

Peritonitis outcomes in patients with HIV and end-stage renal failure on peritoneal dialysis: a prospective cohort study.

BACKGROUND: Few studies have investigated the management of human immunodeficiency virus (HIV)-associated end-stage renal failure particularly in low-resource settings with limited access to renal replacement therapy. We aimed to evaluate the effects of HIV infection on continuous ambulatory peritoneal dialysis (CAPD)-associated peritonitis outcomes and technique failure in highly active antiretroviral therapy (HAART)-treated HIV-positive CAPD populations. METHODS: We conducted a single-center prospective cohort study of consecutive incident CAPD patients recruited from two hospitals in Durban, South Africa from September 2012-February 2015. Seventy HIV-negative and 70 HIV-positive end-stage renal failure patients were followed monthly for 18 months at a central renal clinic. Primary outcomes of peritonitis and catheter failure were assessed for the first 18 months of CAPD therapy. We assessed risk factors for peritonitis and catheter failure using Cox regression survival analysis. RESULTS: The HIV-positive cohort had a significantly increased rate of peritonitis compared to the HIV-negative cohort (1.86 vs. 0.76 episodes/person-years, respectively; hazard ratio [HR], 2.41; 95% confidence interval [CI], 1.69-3.45, P < 0.001). When the baseline CD4 count was below 200 cells/µL, the peritonitis rate rose to 3.69 episodes/person-years (HR 4.54, 95% CI 2.35-8.76, P < 0.001), while a baseline CD4 count above 350 cells/µL was associated with a peritonitis rate of 1.60 episodes/person-years (HR 2.10, CI 1.39-3.15, P = 0.001). HIV was associated with increased hazards of peritonitis relapse (HR, 3.88; CI, 1.37-10.94; P = 0.010). Independent predictors associated with increased peritonitis risk were HIV (HR, 1.84; CI, 1.07-3.16; P = 0.027), diabetes (HR, 2.09; CI, 1.09-4.03; P = 0.027) and a baseline CD4 count < 200 cells/µL (HR, 3.28; CI, 1.42-7.61; P = 0.006). Catheter failure rates were 0.34 (HIV-positive cohort) and 0.24 (HIV-negative cohort) episodes/person-years (HR, 1.42; 95% CI, 0.73-2.73; P = 0.299). Peritonitis (HR, 14.47; CI, 2.79-75.00; P = 0.001), average hemoglobin concentrations (HR, 0.75; CI, 0.59-0.95; P = 0.016), and average serum C-reactive protein levels were independent predictors of catheter failure. CONCLUSIONS: HIV infection in end-stage renal disease patients managed by CAPD was associated with increased peritonitis risk; however, HIV infection did not increase the risk for CAPD catheter failure rate at 18 months.

Cytomegalovirus retinitis and antiretroviral treatment: A fifteen year experience.

Background: South Africa's public antiretroviral treatment (ART) programme has undergone progressive changes since its introduction in 2004. The effect of this on the burden of the AIDS-defining opportunistic infection, cytomegalovirus retinitis (CMVR), in SA, has not been fully appreciated. Objectives: To determine the effect of ART availability in the public sector of SA on the trend in the number of cases of newly diagnosed CMVR over time. Methods: This is a retrospective study from 01 November 2002 to 31 August 2017 that took place at a tertiary hospital in the KwaZulu-Natal (KZN) province. Results: A total of 383 participants were included in the study, with 60.1% being female and 94% of black African origin. The mean age of patients was 34.08 years (SD ± 7.24). A linear trend model suggested an overall linear decrease in the number of new cases of CMVR per year (R 2 of 0.67). The average number of new cases of CMVR per year prior to ART being available to all persons living with HIV (PLWH) with a CD4+ ≤ 350 cells/µL and after was 34 and 13, respectively, and the difference (61.76%) between these values was statistically significant, P = 0.001. The median CD4+ count at diagnosis of CMVR was 22 (interquartile range: 9-51.25) cells/µL. An overall 51% of patients in this study were on ART at diagnosis of CMVR. There was a higher proportion of patients on ART ≤ 6 months (63.3%), compared with those on ART > 6 months (36.7%), and the difference was statistically significant, P < 0.01. Conclusion: ART has resulted in a decrease in the burden of CMVR on ophthalmic services for many in KZN, particularly following the introduction of ART for all PLWH with a CD4 ≤ 350 cells/µL.

Mucocutaneous diseases in the combined antiretroviral therapy era: prevalence and spectrum in HIV seropositive children and adolescents in Durban, South Africa.

BACKGROUND: Mucocutaneous diseases (MCD) have been commonly described among human immunodeficiency virus (HIV) infected patients before the combined antiretroviral therapy (cART) era. There is limited data on the frequency and type of MCD in the cART era in African children and adolescents. This study aimed to describe the prevalence and spectrum of MCD in South African children and adolescents seropositive for HIV on cART. METHODS: A cross-sectional study of 310 participants aged 0-19 years attending a public sector ART clinic at King Edward VIII Hospital, Durban, South Africa, was conducted. Demographic, clinical, and laboratory information was obtained from the participants and hospital records. Participants were examined. Data were collated and analyzed with SPSS version 23. RESULTS: MCD were observed in 77.4% of HIV-infected children. The prevalence was higher among males and adolescents above 16 years old (83.9%). Infectious skin disorders (44.7%) were less common than noninfectious dermatoses (55.3%). More common disorders encountered included generalized pruritus (32.6%), fungal infections (20.9%), and inflammatory (20.4%) and pigmentary (20.4%) skin disorders. Tinea capitis and pedis were the most prevalent fungal infections, while oral candidiasis (0.2%) was the least. Inflammatory skin disorders and dyschromia appeared to be more common than in the pre-cART era. CONCLUSIONS: While MCD are still common in HIV-infected children and adolescents in the cART era, the pattern and types of disorders have changed to a predominance of non-infectious dermatoses.

The knowledge, attitudes and practices of doctors, pharmacists and nurses on antimicrobials, antimicrobial resistance and antimicrobial stewardship in South Africa.

BACKGROUND: Sustained injudicious and indiscriminate use of antimicrobials has exerted selection pressure for developing antimicrobial resistance (AMR), requiring behaviour change from healthcare professionals (HCPs) based on their knowledge, attitudes and practices (KAP) on antimicrobials, AMR and antimicrobial stewardship (AMS). METHODS: A cross-sectional online questionnaire-based survey was conducted nationally amongst doctors, pharmacists and nurses from November 2017 to January 2018. The questionnaire comprised demographic information and KAP questions. RESULTS: Respondents comprised of 1120 doctors, 744 pharmacists and 659 nurses. Antimicrobial resistance was considered a severe problem globally and nationally by majority of HCPs. Self-assessment of knowledge revealed gaps in understanding of antimicrobials, AMR and AMS. Confidence scores in prescribing by doctors, pharmacists and nurses were 57.82%, 32.88% and 45.28%, respectively. Doctors, 441 (45.2%) indicated no confidence in using combination therapy. Prescribing correctly showed a confidence level of 33.99% from 436 doctors, 41.88% from nine pharmacists and 35.23% from 107 nurses. Healthcare professionals (1600 [91.22%]) stated educational campaigns would combat AMR. Only 842 (40.13%) HCPs attended training on these topics and 1712 (81.60%) requesting more education and training. CONCLUSION: This is the first comparative survey on KAP of practising doctors, pharmacists and nurses in South Africa. Doctors had the highest knowledge score followed by nurses and pharmacists. Practice scores did not corroborate knowledge and the higher attitude scores. Gaps in KAP were evident. Healthcare professionals indicated the need for more education and training, thus requiring a review of pre-service and in-service education and training in addition to continued professional development programmes for practising HCPs.

The effect of lifestyle modification on depression among myocardial infarction patients after revascularisation.

BACKGROUND: Patients with coronary artery disease (CAD) are prone to depression, and its presence is associated with poor adverse cardiac outcomes. Although lifestyle modification (LSM) has been shown to be beneficial in managing depression in patients with CAD, it is not known whether the mode of cardiac intervention [(coronary artery bypass graft surgery (CABG) versus percutaneous coronary intervention (PCI)] influences the outcome. OBJECTIVES: We examined the prevalence of depression among myocardial infarction (MI) patients after revascularisation and compared the effect of LSM on incidence of depression in patients who underwent CABG versus PCI. METHODS: We evaluated the risk-factor profile, depression characteristics and lifestyle changes of 100 consecutive participants undergoing coronary revascularisation over a 15-month period (January 2017 to May 2018). The Beck depression inventory II (BDI-II) was used to assess depression and the Goldin leisure-time exercise (GLTE) questionnaire to assess physical activity (PA). RESULTS: One hundred patients were recruited (mean age: males 60.73 ± 4.52 years, females 60.29 ± 3.64 years) but five dropped out, leaving 95 patients for complete analysis. Most of the patients were low-income earners [53 (53.0%)], and 21 (21.0%) had tertiary-level education. The majority had multiple CAD risk factors and co-morbidities (79.0%). Prior to the LSM programme, 51 patients (51.0%) had depression and depressive traits [CABG 34 (66.7%) vs PCI 17 (33.3%), p = 0.047]. After LSM the overall prevalence of depression and depressive traits fell to 33 patients (34.7%) [PCI eight (23.0%) vs CABG 25 patients (72.0%), p = 0.001]. The mean depression scores also fell from 21.11 ± 7.75 to 14.98 ± 9.61 (p = 0.002). At baseline, PCI patients were more physically active compared to CABG patients [three (60.0%) vs two patients (40.0%), respectively, p = 0.715]. After LSM, more PCI patients undertook PA compared to CABG subjects [24 (60.0%) vs 14 patients (35.0%), respectively, p = 0.012]. The PA score was also higher among the PCI group compared to the CABG group [14.16 ± 9.73 vs 9.40 ± 10.94, respectively, p = 0.024]. In fully compliant subjects, the benefit derived was similar regardless of the mode of intervention [OR 1.10, 95% CI: 0.78-4.23, p = 0.191]. Using multivariate analysis, the main predictors of depression and depressive traits were female gender (OR 3.29, 95% CI: 1.51-11.03, p = 0.008), CABG (OR 1.86, 95% CI: 1.68-5.77, p = 0.003), heart failure (OR 2.65, 95% CI: 5.87-13.62, p = 0.000), kidney failure (OR 1.41, 95% CI: 1.30-5.23, p = 0.041), atrial fibrillation (OR 1.60, 95% CI: 1.40-4.77, p = 0.023), low PA (OR 1.97, 95%, CI: 11.23-33.20, p = 0.000), previous history of depression (OR 8.99, 95% CI: 1.90-7.89, p = 0.002) and low income (OR 2.21, 95% CI: 1.40-2.85, p = 0.000). CONCLUSIONS: Depression and depressive traits are common among subjects undergoing coronary revascularisation, more so among CABG than PCI participants. LSM reduced the prevalence of depression and depressive traits, with fully compliant CABG versus PCI groups deriving nearly the same benefits from the LSM regime. No significant reduction in incidence of depression was recorded among LSM partly compliant patients. This study suggests that failure to implement lifestyle changes and engage in PA are major barriers to managing depression after coronary revascularisation.

The role of human immunodeficiency virus in the pathogenesis of vernal keratoconjunctivitis-like disease in adults: A demographic and epidemiological study.

Purpose: The purpose was to identify and describe patients with new-onset vernal keratoconjunctivitis-like (VKC-like) disease after puberty. Methods: The study consisted of two parts: a prospective observational descriptive study of patients with new-onset VKC-like disease, and a case-control study to determine the relationship of a CD4 count with VKC-like disease in adults, in the setting of human immunodeficiency virus (HIV). Patients were recruited between January 2016 and November 2017 from a Provincial Eye hospital, one of two large referral hospitals in KwaZulu-Natal, South Africa. Patients presenting to the eye clinic were screened and diagnosed at the Primary Eye Care Unit. Inclusion criteria: age 15 years and older with signs and symptoms of new-onset VKC-like disease. Exclusion criteria: a history of childhood atopic diseases, atopic keratoconjunctivitis and patients who declined HIV testing. Data collected included HIV status, CD4 count, antinuclear antibodies and total serum immunoglobulin E. Results: Thirty-three patients were included; females n = 16 and males n = 17. The mean age at presentation was 32.45 ± 9.93 years, 95% CI = 28.94-35.97. Twenty-six patients (78.8%) were HIV positive, 95% CI (62-89). The proportion of HIV positive patients was statistically different from the HIV negative group, Chi-squared = 21.866, P value <0.0001. In the group of HIV positive patients, 72% were classified as immunodeficient according to their CD4 counts. An association was proven between severely immunodeficient patients and the risk of VKC-like disease (Chi-squared = 4.992, P value = 0.0255). Conclusion: In this cohort, a statistically significant association was found between VKC-like disease in adults and an HIV positive status. This association calls for more research on the subject.

rpoB Mutations Causing Discordant Rifampicin Susceptibility in Mycobacterium tuberculosis: Retrospective Analysis of Prevalence, Phenotypic, Genotypic, and Treatment Outcomes.

BACKGROUND: Discordant genotypic/phenotypic rifampicin susceptibility testing in Mycobacterium tuberculosis is a significant challenge, yet there are limited data on its prevalence and how best to manage such patients. Whether to treat isolates with rpoB mutations not conferring phenotypic resistance as susceptible or multidrug-resistant tuberculosis (MDR-TB) is unknown. We describe phenotypic and genotypic characteristics of discordant isolates and clinical characteristics and treatment outcomes of affected patients in KwaZulu-Natal, South Africa. METHODS: We analyzed clinical isolates showing rifampicin resistance on GenoType MTBDRplus while susceptible on 1% agar proportion method. We measured rifampicin minimum inhibitory concentrations (MICs) using Middlebrook 7H10 agar dilution and BACTEC MGIT 960. Sensititre MYCOTB plates were used for drug-susceptibility testing, and rpoB gene sequencing was performed on all isolates. Local MDR-TB program data were reviewed for clinical information and patient outcomes. RESULTS: Discordant isolates constituted 4.6% (60) of 1302 rifampicin-resistant cases over the study period. Of these, 62% remained susceptible to isoniazid and 98% remained susceptible to rifabutin. Rifampicin MICs were close to the critical concentration of 1 µg/mL (0.5-2 µg/mL) for 83% of isolates. The most frequent rpoB mutations were Q513P (25.3%), D516V (19.2%), and D516Y (13.3%). Whereas 70% were human immunodeficiency virus infected, the mean CD4 count was 289 cells/mm3 and 87% were receiving antiretroviral therapy. Standard therapy for MDR-TB was used and 53% achieved successful treatment outcomes. CONCLUSIONS: Rifampicin-discordant TB is not uncommon and sequencing is required to confirm results. The high susceptibility to rifabutin and isoniazid and poor treatment outcomes with the current regimen suggest a potential utility for rifabutin-based therapy.

Opening the black box of neural networks: methods for interpreting neural network models in clinical applications.

Artificial neural networks (ANNs) are powerful tools for data analysis and are particularly suitable for modeling relationships between variables for best prediction of an outcome. While these models can be used to answer many important research questions, their utility has been critically limited because the interpretation of the "black box" model is difficult. Clinical investigators usually employ ANN models to predict the clinical outcomes or to make a diagnosis; the model however is difficult to interpret for clinicians. To address this important shortcoming of neural network modeling methods, we describe several methods to help subject-matter audiences (e.g., clinicians, medical policy makers) understand neural network models. Garson's algorithm describes the relative magnitude of the importance of a descriptor (predictor) in its connection with outcome variables by dissecting the model weights. The Lek's profile method explores the relationship of the outcome variable and a predictor of interest, while holding other predictors at constant values (e.g., minimum, 20th quartile, maximum). While Lek's profile was developed specifically for neural networks, partial dependence plot is a more generic version that visualize the relationship between an outcome and one or two predictors. Finally, the local interpretable model-agnostic explanations (LIME) method can show the predictions of any classification or regression, by approximating it locally with an interpretable model. R code for the implementations of these methods is shown by using example data fitted with a standard, feed-forward neural network model. We offer codes and step-by-step description on how to use these tools to facilitate better understanding of ANN.

Social support and coping in adults with type 2 diabetes.

BACKGROUND: The diagnosis of diabetes has been described as a lifelong psychological burden on the patient and his or her family. Social support plays a pivotal role in patients with diabetes and is important in enabling them to cope effectively with the disease. There is a dearth of research on social support and coping in patients with diabetes in South Africa. OBJECTIVES: The aim of this study was to explore whether patients with poor perceived social support have lower levels of well-being and coping than patients with good social support. METHOD: A cross-sectional study was conducted at both public and private facilities on the north coast of KwaZulu-Natal, South Africa. The Diabetes Care Profile (DCP), the General Health Questionnaire (GHQ), the Social Support Questionnaire (SSQ) and the WHO-5 Well-being Index (WHO-5) were administered to 401 participants. RESULTS: The findings indicate that there is an inverse relationship between social support and coping, which suggests that an increase in social support is associated with a decrease in emotional distress. There was a small positive correlation between the SSQ and the WHO-5, which suggests participants who had good support endorsed better levels of well-being. Although participants indicated that they were satisfied with their level of support, they had poor coping as indicated by the high mean score on the GHQ and the high HbA1c level. There was a small positive correlation between GHQ and HbA1c. There was no association between social support and HbA1c. CONCLUSION: Social support is important in helping the patient with diabetes cope with the disease and to improve adherence to treatment. Health care providers should take cognisance of psychosocial factors in the treatment regime of the patient. Family members should be educated about diabetes, the importance of adherence and long-term complications of the disease.

Sequential design of a novel PVA-based crosslinked ethylenic homopolymer for extended drug delivery.

A Box-Behnken Design was employed to study the influence of boric acid, sodium sulfate, ammonia and n-propanol in the formulation of crosslinked ethylenic homopolymeric (CEH) gelispheres from native polyvinyl alcohol (PVA). The dependent variables studied included the size of the spherical gelispheres, drug encapsulation efficiency, in vitro dissolution after 30 min and textural parameters, namely fracture force and matrix rupture energy. Based on these responses, an optimized CEH gelisphere matrix was formulated and thereafter incorporated as a powder into a candidate crosslinked zinc-pectinate multiple-unit device to assess its effect on modifying drug release. In the case of the CEH-loaded zinc-pectinate gelispheres, it was determined via constrained optimization that a maximum drug encapsulation efficiency of 28.63% could be obtained under the conditions of 0% (w/v) CEH, 13 h of crosslinking and drying temperature of 60 degrees C. On the other hand, initial drug release could be significantly retarded when 0.10% (w/v) of CEH was included in the formulation and crosslinked for 24 h at 40 degrees C. In this regard, CEH induced a 4 h lag phase. Furthermore, zero-order drug release was produced and could be maintained over several weeks. Kinetic analysis of drug release further supported that CEH inhibits polymer relaxation (k2<

Experimental design for the formulation and optimization of novel cross-linked oilispheres developed for in vitro site-specific release of Mentha piperita oil.

A Plackett-Burman design was employed to develop and optimize a novel crosslinked calcium-aluminum-alginate-pectinate oilisphere complex as a potential system for the in vitro site-specific release of Mentha piperita, an essential oil used for the treatment of irritable bowel syndrome. The physicochemical and textural properties (dependent variables) of this complex were found to be highly sensitive to changes in the concentration of the polymers (0%-1.5% wt/vol), crosslinkers (0%-4% wt/vol), and crosslinking reaction times (0.5-6 hours) (independent variables). Particle size analysis indicated both unimodal and bimodal populations with the highest frequency of 2 mm oilispheres. Oil encapsulation ranged from 6 to 35 mg/100 mg oilispheres. Gravimetric changes of the crosslinked matrix indicated significant ion sequestration and loss in an exponential manner, while matrix erosion followed Higuchi's cube root law. Among the various measured responses, the total fracture energy was the most suitable optimization objective (R2 = 0.88, Durbin-Watson Index = 1.21%, Coefficient of Variation (CV) = 33.21%). The Lagrangian technique produced no significant differences (P > .05) between the experimental and predicted total fracture energy values (0.0150 vs 0.0107 J). Artificial Neural Networks, as an alternative predictive tool of the total fracture energy, was highly accurate (final mean square error of optimal network epoch approximately 0.02). Fused-coated optimized oilispheres produced a 4-hour lag phase followed by zero-order kinetics (n > 0.99), whereby analysis of release data indicated that diffusion (Fickian constant k1 = 0.74 vs relaxation constant k2 = 0.02) was the predominant release mechanism.