Influence of vitamin D supplementation on growth, body composition, pubertal development and spirometry in South African schoolchildren: a randomised controlled trial (ViDiKids).

OBJECTIVE: To determine whether weekly oral vitamin D supplementation influences growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. DESIGN: Phase 3 double-blind randomised placebo-controlled trial. SETTING: Socioeconomically disadvantaged peri-urban district of Cape Town, South Africa. PARTICIPANTS: 1682 children of black African ancestry attending government primary schools and aged 6-11 years at baseline. INTERVENTIONS: Oral vitamin D3 (10 000 IU/week) versus placebo for 3 years. MAIN OUTCOME MEASURES: Height-for-age and body mass index-for-age, measured in all participants; Tanner scores for pubertal development, spirometric lung volumes and body composition, measured in a subset of 450 children who additionally took part in a nested substudy. RESULTS: Mean serum 25-hydroxyvitamin D3 concentration at 3-year follow-up was higher among children randomised to receive vitamin D versus placebo (104.3 vs 64.7 nmol/L, respectively; mean difference (MD) 39.7 nmol/L, 95% CI 37.6 to 41.9 nmol/L). No statistically significant differences in height-for-age z-score (adjusted MD (aMD) -0.08, 95% CI -0.19 to 0.03) or body mass index-for-age z-score (aMD -0.04, 95% CI -0.16 to 0.07) were seen between vitamin D versus placebo groups at follow-up. Among substudy participants, allocation to vitamin D versus placebo did not influence pubertal development scores, % predicted forced expiratory volume in 1 s (FEV1), % predicted forced vital capacity (FVC), % predicted FEV1/FVC, fat mass or fat-free mass. CONCLUSIONS: Weekly oral administration of 10 000 IU vitamin D3 boosted vitamin D status but did not influence growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov NCT02880982, South African National Clinical Trials Register DOH-27-0916-5527.

Influence of vitamin D supplementation on bone mineral content, bone turnover markers, and fracture risk in South African schoolchildren: multicenter double-blind randomized placebo-controlled trial (ViDiKids).

Randomized controlled trials (RCTs) to determine the influence of vitamin D on BMC and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n = 450) nested within a phase 3 RCT of weekly oral supplementation with 10 000 IU vitamin D3 vs placebo for 3 yr in HIV-uninfected Cape Town schoolchildren aged 6-11 yr. Outcomes were BMC at the whole body less head (WBLH) and LS and serum 25-hydroxyvitamin D3 (25(OH)D3), PTH, alkaline phosphatase, C-terminal telopeptide, and PINP. Incidence of fractures was a secondary outcome of the main trial (n = 1682). At baseline, mean serum 25(OH)D3 concentration was 70.0 nmol/L (SD 13.5), and 5.8% of participants had serum 25(OH)D3 concentrations <50 nmol/L. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI, 36.1 to 43.6) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI, -0.94 to -0.17). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI, -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI, -1.3 to 0.8) or serum concentrations of bone turnover markers. Fractures were rare among participants in the main trial randomized to vitamin D vs placebo (7/755 vs 10/758 attending at least 1 follow-up; adjusted odds ratio 0.70, 95% CI, 0.27 to 1.85). In conclusion, a 3-yr course of weekly oral vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC or serum concentrations of bone turnover markers. Fracture incidence was low, limiting power to detect an effect of vitamin D on this outcome.

Vitamin D­the "sunshine vitamin"­is essential for helping the body to absorb calcium from the diet, which is laid down in bone to improve its strength. There is a lack of clinical trials testing whether vitamin D supplements can improve bone content of calcium and other minerals, or reduce risk of bone fractures (broken bones) in children of Black African ancestry. We therefore conducted such a study, recruiting 1682 schoolchildren aged 6­11 yr living in Cape Town, South Africa. We found that a weekly dose of 10 000 international units (250 micrograms) of vitamin D3, given by mouth for 3 yr, was effective in boosting vitamin D levels in trial participants who received it. However, this did not have any effect on bone content of calcium and other minerals. Relatively few children experienced a broken bone during the study, so we were unable to say with confidence whether or not vitamin D supplements might affect this outcome.

A descriptive study of vancomycin use at Red Cross War Memorial Children's Hospital, Cape Town.

Background: Antimicrobial stewardship principles guide the clinical use of antimicrobials, including vancomycin, but paediatric vancomycin prescribing practices have not been evaluated in South Africa. Objectives: To document the use, prescribing practices and monitoring of intravenous vancomycin and the spectrum of bacteria isolated on microbiological culture in children treated with intravenous vancomycin during a 12-month period at Red Cross War Memorial Children's Hospital (RCWMCH). Method: A retrospective audit of intravenous vancomycin use in children admitted to RCWMCH during 2019 was performed. Results: All 158 vancomycin prescription episodes for 143 children were included. Overall usage of intravenous vancomycin was 63 days of therapy per 1000 patient days (interquartile range [IQR]: 38-72). The median starting dose was 15 mg/kg per dose (IQR: 14-15) and median daily dose was 45 mg/kg per day (IQR: 43-60). Vancomycin was prescribed as empiric (127/158, 80%) and directed (31/158, 20%) treatment. The median duration of treatment for the directed group (7 days) was longer than the empiric group (4 days) (p = 0.001). Vancomycin serum trough concentrations were performed in 65/98 (66%) episodes where vancomycin treatment exceeded 3 days, with only 16/65 (25%) of these samples obtained before the fourth dose. Prolonged antibiotic treatment of 14 days or more was not associated with Gram-positive bacteria on culture (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 0.17-4.2). Conclusion: Dosing errors, prolonged empiric treatment and inappropriate vancomycin monitoring were problems associated with vancomycin prescriptions. Contribution: The study identified multiple opportunities for improved vancomycin prescribing and monitoring. Further research and implementation of improved prescribing practices could contribute to the preservation of vancomycin as an effective antibiotic.

Vitamin D supplementation to prevent tuberculosis infection in South African schoolchildren: multicenter phase 3 double-blind randomized placebo-controlled trial (ViDiKids).

OBJECTIVES: To determine whether weekly oral supplementation with 10,000 IU vitamin D3 for 3 years reduces the risk of sensitization to M. tuberculosis in South African schoolchildren aged 6-11 years with negative QuantiFERON-tuberculosis (TB) Gold Plus (QFT-Plus) assay results at baseline. METHODS: We conducted a phase 3 randomized placebo-controlled trial in 1682 children attending 23 primary schools in Cape Town. The primary outcome was a positive end-trial QFT-Plus result, analyzed using a mixed effects logistic regression model with the school of attendance included as a random effect. RESULTS: 829 vs. 853 QFT-Plus-negative children were randomized to receive vitamin D3 vs. placebo, respectively. Mean end-study 25(OH)D concentrations in participants randomized to vitamin D vs. placebo were 104.3 vs 64.7 nmol/l, respectively (95% confidence interval for difference, 37.6 to 41.9 nmol/l). A total of 76/667 (11.4%) participants allocated to vitamin D vs. 89/687 (13.0%) participants allocated to placebo tested QFT-Plus positive at 3-year follow-up (adjusted odds ratio 0.86, 95% confidence interval 0.62-1.19, P = 0.35). CONCLUSION: Weekly oral supplementation with 10,000 IU vitamin D3 for 3 years elevated serum 25(OH)D concentrations among QFT-Plus-negative Cape Town schoolchildren but did not reduce their risk of QFT-Plus conversion.

Candida bloodstream infection among children hospitalised in three public-sector hospitals in the Metro West region of Cape Town, South Africa.

BACKGROUND: Candida bloodstream infection (BSI) causes appreciable mortality in neonates and children. There are few studies describing the epidemiology of Candida BSI in children living in sub-Saharan Africa. METHODS: A retrospective descriptive study was conducted at three public sector hospitals in Cape Town, South Africa. Demographic and clinical details, antifungal management and patient outcome data were obtained by medical record review. Candida species distribution and antifungal susceptibility testing results were obtained from the National Health Laboratory Service database. RESULTS: Of the 97 Candida BSI episodes identified during a five-year period, 48/97 (49%) were Candida albicans (C. albicans), and 49/97 (51%) were non-C. albicans species. The overall incidence risk was 0.8 Candida BSI episodes per 1000 admissions at Red Cross War Memorial Children's Hospital. Of the 77/97 (79%) Candida BSI episodes with available clinical information, the median age (interquartile range) at the time of BSI was 7 (1-25) months, 36/77 (47%) were associated with moderate or severe underweight-for-age and vasopressor therapy was administered to 22/77 (29%) study participants. Most of the Candida BSI episodes were healthcare-associated infections, 63/77 (82%). Fluconazole resistance was documented among 17%, 0% and 0% of C. parapsilosis, C. tropicalis and C. albicans isolates, respectively. All Candida isolates tested were susceptible to amphotericin B and the echinocandins. The mortality rate within 30 days of Candida BSI diagnosis was 13/75 (17%). On multivariable analysis, factors associated with mortality within 30 days of Candida BSI diagnosis included vasopressor therapy requirement during Candida BSI, adjusted Odds ratio (aOR) 53 (95% confidence interval 2-1029); hepatic dysfunction, aOR 13 (95% CI 1-146); and concomitant bacterial BSI, aOR 10 (95% CI 2-60). CONCLUSION: The study adds to the limited number of studies describing paediatric Candida BSI in sub-Saharan Africa. Non-C. Albicans BSI episodes occurred more frequently than C. albicans episodes, and vasopressor therapy requirement, hepatic dysfunction and concomitant bacterial BSI were associated with an increase in 30-day mortality.

Hospitalization among infants who initiate antiretroviral therapy before 3 months of age.

INTRODUCTION: Studies examining hospitalization among infants with HIV in resource-limited settings, in the context of early infant diagnosis and early antiretroviral therapy (ART) initiation, are limited. METHODS: We used routinely collected data on infants who initiated ART aged <3 months (Western Cape province, South Africa; 2013-2017) to describe hospitalization from birth until 12 months post-ART initiation. Record reviews were additionally performed at three tertiary-level facilities. We used mixed-effects Poisson regression to examine factors associated with hospitalization. RESULTS: Among 840 infants, 579 (69%) were hospitalized; 36% had >1 hospitalization. Median age at ART initiation decreased from 57 days (interquartile range [IQR] 22-74; 2013-2015) to 19 days (IQR 5-54; 2016-2017). Early neonatal hospitalization (age <7 days) occurred in 271 infants (32%) and represented 24% of hospitalizations (272/1131). Overall, 443 infants (53%) were hospitalized at age ≥7 days, including 13% with hospitalizations pre-ART initiation, 15% pre and post-ART initiation and 25% post-ART initiation. Excluding early neonatal hospitalizations, initiating ART at older age vs. age <1 week was associated with higher hospitalization rates: adjusted incidence rate ratios (95% confidence interval) were 1.86 (1.31-2.64); 2.31 (1.62-3.29) and 2.47 (1.76-3.46) if ART initiation age was 1-4 weeks; 5-8 weeks and 9-12 weeks respectively. Among infants whose hospital records were reviewed, reasons for early neonatal hospitalizations mostly related to prematurity or low birthweight (n = 46/60; 77%) whereas hospitalizations at age ≥7 days were mostly due to infections (n = 206/243; 85%). CONCLUSIONS: Earlier ART initiation is associated with lower hospitalization rates. High hospitalization rates, despite initiation age <3 months, is concerning.

Descriptive analysis of infections due to New Delhi metallo-ß-lactamase-producing Enterobacterales in children at Red Cross War Memorial Children's Hospital.

The increased incidence and absence of antibiotic treatment options for New Delhi metallo-ß-lactamase (NDM)-producing carbapenem-resistant Enterobacterales (CRE) infection are concerning. Recent reports have highlighted NDM-producing Serratia marcescens, as a specific concern, as it is an organism which is intrinsically resistant to colistin. In this study, a descriptive analysis of NDM-producing CRE infections was performed at the Red Cross War Memorial Children's Hospital.

Balamuthia mandrillaris Granulomatous Amoebic Encephalitis: The First African Experience.

We report the first case of Balamuthia mandrillaris granulomatous amoebic encephalitis definitively acquired in Africa. Our case emphasizes initial nonspecific dermatological features, delays in confirmation of the diagnosis, difficulties accessing recommended medication, and uncertainty about optimal treatment of a disease with a frequently fatal outcome.

Xpert MTB/RIF Ultra and mycobacterial culture in routine clinical care at a paediatric hospital.

Background: Microbiological confirmation of pulmonary tuberculosis (PTB) in children is a well-documented challenge. This study evaluated Xpert Mycobacterium Tuberculosis (MTB)/Rifampicin (RIF) Ultra (Ultra) and mycobacterial cultures in routine clinical care at a tertiary paediatric hospital. Methods: Children treated for PTB and who had at least one respiratory specimen investigated by Ultra and mycobacterial culture before tuberculosis (TB) treatment was commenced were included. The findings of this retrospective study were summarised using descriptive and inferential statistics. Results: A total of 174 children were included. The median age was 2.5 years. Microcytic anaemia, airway compression, cavitary disease and miliary TB were significantly observed in children with microbiologically confirmed TB (cTB). Tuberculosis was microbiologically confirmed in 93 (53.4%) children. The positive yield from testing the first respiratory specimens was 68/174 (39.1%) on Ultra and 82/174 (47.1%) on combined Ultra and mycobacterial culture. In the subset of children (n = 70) tested with Ultra on two sequential respiratory specimens, the incremental yield from the second specimen was 30.3%. In the subset of children (n = 16) tested with Ultra on three sequential respiratory specimens, the incremental yield from the second and third specimens was 16.7% and 0.0%, respectively. When Ultra and mycobacterial culture results were combined, the incremental yield in children who had two sequential respiratory specimens tested was 24.4% and 3.1% on Ultra and mycobacterial culture, respectively. Conclusion: Ultra and mycobacterial culture on a single respiratory specimen resulted in a high microbiological yield. Ultra-testing on a second respiratory specimen increased the yield of microbiologically cTB. Additional diagnostic testing may require further study.

Prevalence and Determinants of Vitamin D Deficiency in 1825 Cape Town Primary Schoolchildren: A Cross-Sectional Study.

Vitamin D deficiency (25-hydroxyvitamin D[25(OH)D] <50 nmol/L) is common among adults in Cape Town, South Africa, but studies investigating vitamin D status of children in this setting are lacking. We conducted a cross-sectional study to determine the prevalence and determinants of vitamin D deficiency in 1825 Cape Town schoolchildren aged 6−11 years. Prevalence of vitamin D deficiency was 7.6% (95% Confidence Interval [CI] 6.5% to 8.9%). Determinants of vitamin D deficiency included month of sampling (adjusted odds ratio [aOR] for July−September vs. January−March 10.69, 95% CI 5.02 to 22.77; aOR for October−December vs. January−March 6.73, 95% CI 2.82 to 16.08), older age (aOR 1.25 per increasing year, 95% CI: 1.01−1.53) and higher body mass index (BMI; aOR 1.24 per unit increase in BMI-for-age Z-score, 95% CI: 1.03−1.49). In a subset of 370 participants in whom parathyroid hormone (PTH) concentrations were measured; these were inversely related to serum 25(OH)D concentrations (p < 0.001). However, no association between participants with hyperparathyroidism (PTH >6.9 pmol/L) and vitamin D deficiency was seen (p = 0.42). In conclusion, we report that season is the major determinant of vitamin D status among Cape Town primary schoolchildren, with prevalence of vitamin D deficiency ranging from 1.4% in January−March to 22.8% in July−September.

Looking back at paediatric HIV treatment in South Africa. My, how we have grown!

Antiretroviral treatment has undergone major changes in the last 20 years, from monotherapy, to dual therapy and finally to triple therapy. Lately, more focus has been placed on better, more well-tolerated combinations and formulations. As in most other disciplines in medicine, the development of paediatric HIV dosages and formulations always tends to lag behind adult research. Twenty years ago, it could take several years before data were available to enable the use of life-saving antiretrovirals in children. Paediatricians, being ever resourceful, were not prepared to let their paediatric patients suffer despite the lack of data or formulations and so made a plan. This article describes some of the trials and tribulations that we went through trying to make sure that our paediatric HIV patients not only survived but thrived. Clinicians treating paediatric patients today have it so much easier because of what our colleagues and their patients went through in those early days.

Development of the first edition of African treatment guidelines for common bacterial infections and syndromes.

Standard treatment guidelines (STGs) are an important tool for ensuring high quality clinical care and prudent antimicrobial use (AMU) and stewardship (AMS). In 2018, African Union (AU) member state representatives recognized the lack of STGs as a barrier to AMS at national and facility levels. Previous research reported that only 17 of 55 (31%) member states had STGs that provided disease- or pathogen-specific antimicrobial treatment recommendations, excluding those that covered only treatment of HIV, malaria, and tuberculosis). The Africa Centres for Disease Control and Prevention convened expert panels to develop first edition antibiotic treatment guidelines for priority infectious diseases and clinical syndromes for pediatric and adult patient populations in Africa. The purpose of the guidelines is to provide healthcare workers with treatment guidance by harmonising existing national STGs, filling gaps where existing STGs are not available, and serving as a model for future guidelines. Two expert panels of 28 total clinicians, pharmacists, and other relevant stakeholders from 14 AU member states representing each continental region convened to develop consensus treatment recommendations for select priority bacterial infections and clinical syndromes. In developing recommendations, the panels considered treatment recommendations from existing STGs, drug availability, clinical experience, and available antimicrobial resistance data. The guidelines underwent an external review process where clinical stakeholders who did not serve on either panel were invited to submit feedback prior to their publication. The guidelines provide empiric antibiotic therapy guidelines - including drug selection, route of administration, formulation, dosage, and therapy duration - and principles of stewardship for 28 bacterial infections or clinical syndromes. The first edition guidelines for the treatment of common infectious diseases and clinical syndromes in Africa aims to improve clinical treatment and antimicrobial stewardship and will serve as a template for future regional guidelines.

Colonisation with extended spectrum beta-lactamase-producing and carbapenem-resistant Enterobacterales in children admitted to a paediatric referral hospital in South Africa.

INTRODUCTION: There are few studies describing colonisation with extended spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and carbapenem-resistant Enterobacterales (CRE) among children in sub-Saharan Africa. Colonisation often precedes infection and multi-drug-resistant Enterobacterales are important causes of invasive infection. METHODS: In this prospective cross-sectional study, conducted between April and June 2017, 200 children in a tertiary academic hospital were screened by rectal swab for EBSL-PE and CRE. The resistance-conferring genes were identified using polymerase chain reaction technology. Risk factors for colonisation were also evaluated. RESULTS: Overall, 48% (96/200) of the children were colonised with at least one ESBL-PE, 8.3% (8/96) of these with 2 ESBL-PE, and one other child was colonised with a CRE (0.5% (1/200)). Common colonising ESBL-PE were Klebsiella pneumoniae (62.5%, 65/104) and Escherichia coli (34.6%, 36/104). The most frequent ESBL-conferring gene was blaCTX-M in 95% (76/80) of the isolates. No resistance- conferring gene was identified in the CRE isolate (Enterobacter cloacae). Most of the Klebsiella pneumoniae isolates were susceptible to piperacillin/tazobactam (86.2%) and amikacin (63.9%). Similarly, 94.4% and 97.2% of the Escherichia coli isolates were susceptible to piperacillin/tazobactam and amikacin, respectively. Hospitalisation for more than 7 days before study enrolment was associated with ESBL-PE colonisation. CONCLUSION: Approximately half of the hospitalised children in this study were colonised with ESBL-PE. This highlights the need for improved infection prevention and control practices to limit the dissemination of these microorganisms.

Pseudomonas aeruginosa bloodstream infection at a tertiary referral hospital for children.

BACKGROUND: This study describes the disease burden, clinical characteristics, antibiotic management, impact of multidrug resistance and outcome of Pseudomonas aeruginosa bloodstream infection (PABSI) among children admitted to a tertiary referral hospital for children in Cape Town, South Africa. METHODS: A retrospective descriptive study was conducted at a paediatric referral hospital in Cape Town, South Africa. Demographic and clinical details, antibiotic management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the National Health Laboratory Service database. RESULTS: The incidence risk of PABSI was 5.4 (95% CI: 4.34-6.54) PABSI episodes / 10,000 hospital admissions and the most common presenting feature was respiratory distress, 34/91 (37.4%). Overall, 69/91 (75.8%) of the PA isolates were susceptible to all antipseudomonal antibiotic classes evaluated. Fifty (54.9%) of the PABSI episodes were treated with appropriate empiric antibiotic therapy. The mortality rate was 24.2% and in multivariable analysis, empiric antibiotic therapy to which PA isolates were not susceptible, infections present on admission, and not being in the intensive care unit at the time that PABSI was diagnosed were significantly associated with 14-day mortality. CONCLUSIONS: PABSI caused appreciable mortality, however, appropriate empiric antibiotic therapy was associated with reduced 14-day mortality.

Quality of life in postostomy surgery patients: A cross-sectional survey.

BACKGROUND AND AIM: Ostomy is a radical treatment that is sometimes required due to severe inflammatory bowel disease (IBD), colorectal cancer (CRC), and so on. Around 8000 people in New Zealand live with stoma bags. We studied factors associated with poor quality of life (QoL) in ostomy patients to improve patient care. METHODS: Eligible adult patients identified through the Southern District Health Board database were invited to participate. The survey consisted of the general stoma QoL, IBD, CRC QoL, and dietary and lifestyle questionnaires. RESULTS: Response rate was 54.5% (n = 241/448). Study participants were a mean (SD) 70.9 (14.2) years old, 60.6% were male, and 89.5% were New Zealand European; 52.5% of the study participants had a colostomy, and 56.4 and 22.4% received their stoma due to CRC and IBD, respectively. Median (first-third interquartile range) duration since ostomy for overall study sample was 6.9 (3.3-15.1) years. Mean (SD) Stoma-QoL score for all the patients was 60.3 (10.8) points (scale 20-80). Stoma-underlying disease (P = 0.28) and type of stoma (P = 0.60) were not associated with Stoma-QoL scores. Older adults had higher Stoma-QoL, IBD questionnaire and QLQ-C30 quality-of-life scores; 73.1% received dietary recommendations for the stoma, And 56.4% changed their diet, 51.4% found it easy to adhere to dietary recommendations, and 9.2% found it quite/very difficult. CONCLUSION: This study found high-quality life scores in postostomy patients and no significant association between the underlying disease, time since ostomy, level of comorbidities, and how the appliance worked, which highlight the multifactorial nature of the quality of life concept and difficulties measuring it.

The initial intravenous treatment of a human immunodeficiency virus-infected child with complicated abdominal tuberculosis.

INTRODUCTION: There is very limited published experience with intravenous (IV) antituberculosis (anti-TB) and antiretroviral therapy (ART) especially in children. We have described a human immunodeficiency virus (HIV)-infected child with complicated abdominal tuberculosis who was initially treated with IV anti-TB and a partially IV ART regimen before transitioning to oral therapy. PATIENT PRESENTATION: A 3-year-old boy presented with hypovolaemic shock with a 3-day history of inability to pass stools, abdominal distension and bile-stained vomiting. Abdominal ultrasound and X-ray showed small-bowel obstruction. Human immunodeficiency virus antibody testing was positive, and Cluster of Differentiation (CD)4+ lymphocyte count was 56 cells/mL (15%). Xpert Mycobacterium tuberculosis (MTB)/Rifampicin (RIF) Ultra and TB culture on induced sputum detected MTB complex sensitive to rifampicin and isoniazid. MANAGEMENT AND OUTCOME: Following laparotomy and closure of bowel perforations, the child was commenced on IV rifampicin, moxifloxacin and amikacin. Amikacin was stopped after 3 days because of nephrotoxicity, and meropenem and IV linezolid were added. After 20 days, ART comprising IV zidovudine, oral lamivudine solution, oral lopinavir/ritonavir solution and additional oral ritonavir solution for super boosting was commenced. By day 40, the patient was well established on oral feeds and was switched to standard oral anti-TB medications. Sputum examined 1 month after starting the treatment was found culture-negative for MTB. After 4 months of treatment, the HIV viral load was < 100 copies/mL. He completed a total of 12 months of anti-TB treatment. CONCLUSION: Despite limited experience and few available IV formulations of standard anti-TB and ARV medications, initial IV therapy may be beneficial for patients in whom oral medication is not an option.

The Pex3-Inp1 complex tethers yeast peroxisomes to the plasma membrane.

A subset of peroxisomes is retained at the mother cell cortex by the Pex3-Inp1 complex. We identify Inp1 as the first known plasma membrane-peroxisome (PM-PER) tether by demonstrating that Inp1 meets the predefined criteria that a contact site tether protein must adhere to. We show that Inp1 is present in the correct subcellular location to interact with both the plasma membrane and peroxisomal membrane and has the structural and functional capacity to be a PM-PER tether. Additionally, expression of artificial PM-PER tethers is sufficient to restore retention in inp1Δ cells. We show that Inp1 mediates peroxisome retention via an N-terminal domain that binds PI(4,5)P2 and a C-terminal Pex3-binding domain, forming a bridge between the peroxisomal membrane and the plasma membrane. We provide the first molecular characterization of the PM-PER tether and show it anchors peroxisomes at the mother cell cortex, suggesting a new model for peroxisome retention.

Affimers as anti-idiotypic affinity reagents for pharmacokinetic analysis of biotherapeutics.

Therapeutic antibodies are the fastest growing class of drugs in the treatment of cancer, and autoimmune and inflammatory diseases that require the concomitant development of assays to monitor therapeutic antibody levels. Here, we demonstrate that the use of Affimer nonantibody binding proteins provides an advantage over current antibody-based detection systems. For four therapeutic antibodies, we used phage display to isolate highly specific anti-idiotypic Affimer reagents, which selectively bind to the therapeutic antibody idiotype. For each antibody target the calibration curves met US Food and Drug Administration criteria and the dynamic range compared favorably with commercially available reagents. Affimer proteins therefore represent promising anti-idiotypic reagents that are simple to select and manufacture, and that offer the sensitivity, specificity and consistency required for pharmacokinetic assays.

A ten-year review of ESBL and non-ESBL Escherichia coli bloodstream infections among children at a tertiary referral hospital in South Africa.

INTRODUCTION: There are few studies describing Escherichia coli (E. coli) bloodstream infection (BSI) among children in Africa, yet E.coli is increasing in importance as a cause of antibiotic resistant infection in paediatric settings. METHODS: In this retrospective, descriptive study aspects of E. coli BSI epidemiology are described over a 10-year period including incidence risk, risk factors for extended-spectrum ß-lactamase (ESBL)-producing E. coli BSI, antibiotic susceptibility of the bacterial isolates and outcome including risk factors for severe disease. RESULTS: There were 583 new E. coli BSI episodes among 217,483 admissions, an overall incidence risk of 2.7 events/1,000 hospital admissions. Of 455 of these E. coli BSI episodes that were analysed, 136 (29.9%) were caused by ESBL-producing isolates. Risk factors for ESBL-producing E. coli BSI included hospitalization in the 28-day period preceding E. coli BSI episodes, having an underlying chronic illness other than HIV infection at the time of the E. coli BSI and having a temperature of 38° Celsius or higher at the time of the E. coli BSI. None of the E. coli isolates were resistant to carbapenems or colistin. The mortality rate was 5.9% and admission to the intensive care unit was required in 12.3% of BSI episodes. Predictors of severe disease included age less than 1 month, hospitalization in the 28-day period preceding E. coli BSI and BSI without a definable focus. CONCLUSIONS: These findings extend our understanding of E. coli BSI in a sub-Saharan African setting, provide useful information that can guide empiric treatment choices for community- and hospital-acquired BSI and help inform prevention strategies.