Publications by authors named "Middelkoop K"

Article Synopsis
  • The study aimed to evaluate if vitamin D supplementation affects grip strength, leg power, cardiorespiratory fitness, and exercise-induced bronchoconstriction (EIB) in South African schoolchildren aged 8-11.
  • Conducted in Cape Town, the study involved 450 children who received either 10,000 IU of vitamin D or a placebo weekly for three years, with various fitness measures assessed at the end of the study.
  • While vitamin D supplementation significantly increased serum 25(OH)D levels, it did not lead to improvements in grip strength, explosive leg power, overall fitness, or reduce the risk of EIB in the participants.
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  • The study focuses on childhood TB infection prevalence, incidence, and risk factors in Cape Town, South Africa, highlighting the importance of understanding TB transmission.
  • Using a large sample of primary school children from high TB burden areas, researchers measured TB infection at baseline and tracked changes over three years through the QFT-Plus test.
  • Findings indicate a high prevalence of TB infection (22.6%) associated with factors like age and household exposure to TB, emphasizing the need for effective contact tracing and early treatment to reduce transmission in the community.
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Introduction: HPTN 083 demonstrated the superiority of long-acting cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre-exposure prophylaxis (PrEP) among cisgender men and transgender women who have sex with men (MSM/TGW). HPTN 083 provided the first opportunity to understand experiences with injectable PrEP in a clinical trial.

Methods: Participants from two US sites (Chicago, IL and Atlanta, GA) and one international site (Rio de Janeiro, Brazil) were purposively sampled for individual qualitative interviews (N = 40), between November 2019 and March 2020, to explore trial experiences, barriers to adherence and other factors that may have impacted study implementation or outcomes.

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Article Synopsis
  • - The study aimed to see if weekly vitamin D supplementation affects growth, body composition, pubertal development, or lung function in South African schoolchildren aged 6-11 years, through a rigorous 3-year double-blind trial.
  • - 1682 children participated, with one group receiving 10,000 IU of vitamin D weekly and a control group receiving a placebo, while growth and health measures were closely monitored.
  • - Results showed that while vitamin D levels increased significantly in the supplemented group, there were no meaningful changes in growth, body composition, or lung function compared to the placebo group.
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  • There is a lack of randomized controlled trials (RCTs) investigating the impact of vitamin D on bone mineral content (BMC) and fracture risk in Black African children, leading to this sub-study among 450 Cape Town schoolchildren aged 6-11.
  • The study found that after a 3-year vitamin D supplementation of 10,000 IU weekly, participants had higher serum vitamin D levels and lower parathyroid hormone (PTH) levels, but no significant differences in BMC or bone turnover markers between the vitamin D and placebo groups.
  • Fractures were infrequent in both the vitamin D and placebo groups, suggesting that while vitamin D supplementation improved some biochemical markers, it did not significantly affect bone density or
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The COVID-19 pandemic renewed interest in airborne transmission of respiratory infections, particularly in congregate indoor settings, such as schools. We modeled transmission risks of tuberculosis (caused by Mycobacterium tuberculosis, Mtb) and COVID-19 (caused by SARS-CoV-2) in South African, Swiss and Tanzanian secondary schools. We estimated the risks of infection with the Wells-Riley equation, expressed as the median with 2.

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Background: The HIV Prevention Trials Network (HPTN) 083 trial showed that long-acting injectable cabotegravir was more effective than tenofovir disoproxil fumarate plus emtricitabine in preventing HIV in cisgender men and transgender women who have sex with men. We aimed to characterise the cohort of transgender women included in HPTN 083.

Methods: HPTN 083 is an ongoing, phase 2b/3, randomised, multicentre, double-blind, double-dummy clinical trial done at 43 sites in seven countries (Argentina, Brazil, Peru, the USA, South Africa, Thailand, and Viet Nam).

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Objectives: To determine whether weekly oral supplementation with 10,000 IU vitamin D 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.

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Background: Chronic non-communicable disease comorbidities are a major problem faced by people living with HIV (PLHIV). Obesity is an important factor contributing to such comorbidities and PLHIV face an elevated risk of obesity. However, there is data paucity on the intersection of obesity and HIV in adolescents and youth living with HIV (AYLHIV) in sub-Saharan Africa.

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Background: The HPTN 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was superior to tenofovir-disoproxil fumarate/emtricitabine for human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP). Integrase strand transfer inhibitor (INSTI) resistance-associated mutations (RAMs) were detected in some participants with HIV infection. We used a low viral load INSTI genotyping assay to evaluate the timing of emergence of INSTI RAMs and assessed whether HIV screening with a sensitive RNA assay would have detected HIV infection before INSTI resistance emerged.

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Background: Ventilation rates are a key determinant of the transmission rate of Mycobacterium tuberculosis and other airborne infections. Targeting infection prevention and control (IPC) interventions at locations where ventilation rates are low and occupancy high could be a highly effective intervention strategy. Despite this, few data are available on ventilation rates and occupancy in congregate locations in high tuberculosis burden settings.

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Article Synopsis
  • Research on social contact patterns is essential for creating age-mixing matrices in infectious disease models, usually focusing on close face-to-face interactions.
  • However, this approach may overlook risks from casual contacts and airborne transmission, particularly in diseases like tuberculosis.
  • In a study from South Africa, it was found that while age mixing patterns are similar for different transmission types, the role of older adults in airborne transmission could be overstated due to lower casual contact rates.
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Objective: Novel approaches are needed to understand and disrupt transmission. In this proof-of-concept study, we investigated the use of environmental air samplings to detect and quantify in different clinic settings in a high-burden area.

Design: Cross-sectional, environmental sampling.

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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.

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Background: Congregate settings, such as healthcare clinics, may play an essential role in Mycobacterium tuberculosis (Mtb) transmission. Using patient and environmental data, we studied transmission at a primary care clinic in South Africa.

Methods: We collected patient movements, cough frequency, and clinical data, and measured indoor carbon dioxide (CO2) levels, relative humidity, and Mtb genomes in the air.

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Article Synopsis
  • * Conducted in a community health center near Cape Town, the study involved 458 ART-experienced PWH, finding that many had limited nutritional diversity in their diets and insufficient engagement in regular physical activity.
  • * Despite most participants recognizing the health benefits of exercise, there was a notable lack of awareness regarding the contributors to obesity and its associated health risks, indicating a need for targeted interventions to address diet and exercise habits in this population as they age. *
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South African adolescents carry a high tuberculosis disease burden. It is not known if schools are high-risk settings for (MTB) transmission. To detect airborne MTB genomic DNA in classrooms.

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Background: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection.

Methods: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks.

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Background: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with men. We characterized HIV infections that occurred in the blinded phase of HPTN 083.

Methods: Retrospective testing included HIV testing, viral load testing, quantification of study drugs, and HIV drug resistance testing.

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Introduction: Tuberculosis (TB) transmission is difficult to measure, and its drivers are not well understood. The effectiveness of infection control measures at healthcare clinics and the most appropriate intervention strategies to interrupt transmission are unclear. We propose a novel approach using clinical, environmental and position-tracking data to study the risk of TB transmission at primary care clinics in TB and HIV high burden settings in sub-Saharan Africa.

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Background: Tuberculosis (TB) remains the leading cause of infectious disease-related death. Recently, a trial of BCG revaccination and vaccination with H4:IC31, a recombinant protein vaccine, in South African adolescents (Aeras C-040-404) showed efficacy in preventing sustained QuantiFERON (QFT) conversion, a proxy for () infection. A phase 1b trial of 84 South African adolescents was conducted, concurrent with Aeras C-040-404, to assess the safety and immunogenicity of H4:IC31, H56:IC31 and BCG revaccination, and to identify and optimize immune assays for identification of candidate correlates of protection in efficacy trials.

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Background: While several studies have assessed the associations between biological factors and tuberculosis (TB) transmission, our understanding of the associations between TB transmission and social and economic factors remains incomplete. We aimed to explore associations between community TB transmission and socio-economic factors within a high TB-HIV burdened setting.

Methods: We conducted a cross-sectional molecular epidemiology study among adult patients attending a routine TB clinic.

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Much remains unknown about transmission. Seminal experimental studies from the 1950s demonstrated that airborne expulsion of droplet nuclei from an infectious tuberculosis (TB) patient is the primary route of transmission. However, these findings did not rule out other routes of is transmission.

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Introduction: People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular disease (CVD). Screening for CVD risk factors is recommended but not routine in South African HIV clinics. We sought to describe the prevalence of CVD risk factors among antiretroviral treatment (ART)-experienced patients in South Africa.

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Article Synopsis
  • - Age-mixing patterns significantly influence the spread of infectious diseases, and estimating these patterns more accurately can help understand diseases like tuberculosis that spread through casual indoor interactions.
  • - Researchers used a social contact survey in South Africa to estimate age-mixing patterns between different types of contacts (close and casual) based on reported time spent in various locations by different age groups.
  • - Results indicated that while close and all contact patterns were similar, casual contacts showed more age-based segregation, highlighting the importance of collecting a broader range of social data to understand interactions related to disease transmission.
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