A 10-year cohort analysis of routine paediatric ART data in a rural South African setting.
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ABSTRACT:
SUBMITTER: Lilian RR
PROVIDER: S-EPMC5197927 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSerum sickness-like reaction (SSLR) is an acute inflammatory condition affecting predominantly children. The pathophysiology remains unclear, but drugs are considered the main trigger.ObjectiveThe aim of this study was to describe the clinical and laboratory features, triggers, and treatment modalities in children diagnosed with SSLR.MethodsWe conducted a 10-year retrospective cohort study including all paediatric patients (0 to 18 years old) with query SSLR referred to the Adverse Drug Reactions Clinic at the Children's Hospital of Western Ontario. Diagnostic criteria included acute skin rash plus joint inflammation with or without fever.ResultsWe included 83 patients (47 females). Age ranged from 11 months to 12 years (mean 3.2 years). Amoxicillin was the trigger in 82.7% of patients. The mean time between the exposure to the triggering drug and the development of the symptoms was 8.5 days. Urticaria-like and Erythema multiforme-like lesions were present in 35% and 38.5% of the cases, respectively. Joint inflammation affecting hands/feet was present in 60%. Pruritus, lip/eye swelling, and fever were reported in 33, 31, and 45% of patients, respectively. The lymphocyte toxicity assay (LTA) showed incremental T-cell toxicity in 32 of 34 patients. Children that received treatment with antihistamines/nonsteroidal anti-inflammatory drugs (NSAIDs) plus oral steroids had a mean recovery time shorter than those treated only with antihistamines/NSAIDs (6 versus 8 days; P=0.09).ConclusionsIn our study, SSLR was mostly triggered by amoxicillin and had a mean time presentation of 8.5 days. Further prospective and well-conducted studies are needed.
| S-EPMC8581535 | biostudies-literature
Project description:Public engagement in priority-setting for health is increasingly recognized as a means to ensure more ethical, inclusive and legitimate decision-making processes, especially in the context of Universal Health Coverage where demands outweigh the available resources and difficult decisions need to be made. Deliberative approaches are often viewed as especially useful in considering social values and balancing trade-offs, however, implementation of deliberative engagement tools for priority-setting is scant, especially in low- and middle-income settings. In order to address this gap, we implemented a context-specific public deliberation tool in a rural community in South Africa to determine priorities for a health services package. Qualitative data were analysed from seven group deliberations using the engagement tool. The analysis focused on understanding the deliberative process, what the participants prioritized, the reasons for these selections and how negotiations took place within the groups. The deliberations demonstrated that the groups often considered curative services to be more important than primary prevention which related to the perceived lack of efficacy of existing health education and prevention programmes in leading to behaviour change. The groups engaged deeply with trade-offs between costly treatment options for HIV/AIDS and those for non-communicable disease. Barriers to healthcare access were considered especially important by all groups and some priorities included investing in more mobile clinics. This study demonstrates that deliberative engagement methods can be successful in helping communities balance trade-offs and in eliciting social values around health priorities. The findings from such deliberations, alongside other evidence and broader ethical considerations, have the potential to inform decision-making with regard to health policy design and implementation.
| S-EPMC8428615 | biostudies-literature
Project description:This report is an overview of requests for biological and environmental monitoring of hazardous chemicals, submitted to the National Institute for Occupational Health, Analytical Services Laboratory for testing from the years 2005 to 2015. The report discusses the nature of tests requested and implications for workers' health and environment, as well as potential impact of the uncertainties associated with monitoring of hazardous chemicals. This is a retrospective, descriptive, qualitative and quantitative audit of all samples received and tests performed retrieved from records of analysis by the laboratory. The study sample consisted of 44,221 samples. The report indicates that throughout the interrogation period the demand for biological monitoring was higher than that for environmental monitoring, with more requests for toxic metals than organic pollutants. Toxic metal testing was highest for mercury, followed by manganese, lead, aluminium and arsenic. The highest number of tests for organic pollutants was conducted for pesticides followed by toluene and xylene. The study has also revealed that the scope of tests requested is rather narrow and does not reflect the broad spectrum of South Africa's industrial diversity. Having identified possible reasons for underutilization, a number of reforms that could enhance the laboratory's performance have been addressed.
| S-EPMC7194147 | biostudies-literature
Project description:Mitochondrial disease can be attributed to both mitochondrial and nuclear gene mutations. It has a heterogeneous clinical and biochemical profile, which is compounded by the diversity of the genetic background. Disease-based epidemiological information has expanded significantly in recent decades, but little information is known that clarifies the aetiology in African patients. The aim of this study was to investigate mitochondrial DNA variation and pathogenic mutations in the muscle of diagnosed paediatric patients from South Africa. A cohort of 71 South African paediatric patients was included and a high-throughput nucleotide sequencing approach was used to sequence full-length muscle mtDNA. The average coverage of the mtDNA genome was 81±26 per position. After assigning haplogroups, it was determined that although the nature of non-haplogroup-defining variants was similar in African and non-African haplogroup patients, the number of substitutions were significantly higher in African patients. We describe previously reported disease-associated and novel variants in this cohort. We observed a general lack of commonly reported syndrome-associated mutations, which supports clinical observations and confirms general observations in African patients when using single mutation screening strategies based on (predominantly non-African) mtDNA disease-based information. It is finally concluded that this first extensive report on muscle mtDNA sequences in African paediatric patients highlights the need for a full-length mtDNA sequencing strategy, which applies to all populations where specific mutations is not present. This, in addition to nuclear DNA gene mutation and pathogenicity evaluations, will be required to better unravel the aetiology of these disorders in African patients.
| S-EPMC3355259 | biostudies-literature
Project description:BackgroundGlobally, as countries move towards universal health coverage (UHC), public participation in decisionmaking is particularly valuable to inform difficult decisions about priority setting and resource allocation. In South Africa (SA), which is moving towards UHC, public participation in decision-making is entrenched in policy documents yet practical applications are lacking. Engagement methods that are deliberative could be useful in ensuring the public participates in the priority setting process that is evidence-based, ethical, legitimate, sustainable and inclusive. Methods modified for the country context may be more relevant and effective. To prepare for such a deliberative process in SA, we aimed to modify a specific deliberative engagement tool - the CHAT (Choosing All Together) tool for use in a rural setting.MethodsDesktop review of published literature and policy documents, as well as 3 focus groups and modified Delphi method were conducted to identify health topics/issues and related interventions appropriate for a rural setting in SA. Our approach involved a high degree of community and policy-maker/expert participation. Qualitative data were analysed thematically. Cost information was drawn from various national sources and an existing actuarial model used in previous CHAT exercises was employed to create the board.ResultsBased on the outcomes, 7 health topics/issues and related interventions specific for a rural context were identified and costed for inclusion. These include maternal, new-born and reproductive health; child health; woman and child abuse; HIV/AIDS and tuberculosis (TB); lifestyle diseases; access; and malaria. There were variations in priorities between the 3 stakeholder groups, with community-based groups emphasizing issues of access. Violence against women and children and malaria were considered important in the rural context.ConclusionThe CHAT SA board reflects health topics/issues specific for a rural setting in SA and demonstrates some of the context-specific coverage decisions that will need to be made. Methodologies that include participatory principles are useful for the modification of engagement tools like CHAT and can be applied in different country contexts in order to ensure these tools are relevant and acceptable. This could in turn impact the success of the implementation, ultimately ensuring more effective priority setting approaches.
| S-EPMC9278606 | biostudies-literature
Project description:Streptococcus pneumoniae (the pneumococcus) carriage precedes invasive disease and influences population-wide strain dynamics, but limited data exist on temporal carriage patterns of serotypes due to the prohibitive costs of longitudinal studies. Here, we report carriage prevalence, clearance and acquisition rates of pneumococcal serotypes sampled from newborn infants bi-weekly from weeks 1 to 27, and then bi-monthly from weeks 35 to 52 in the Gambia. We used sweep latex agglutination and whole genome sequencing to serotype the isolates. We show rapid pneumococcal acquisition with nearly 31% of the infants colonized by the end of first week after birth and quickly exceeding 95% after 2 months. Co-colonization with multiple serotypes was consistently observed in over 40% of the infants at each sampling point during the first year of life. Overall, the mean acquisition time and carriage duration regardless of serotype was 38 and 24 days, respectively, but varied considerably between serotypes comparable to observations from other regions. Our data will inform disease prevention and control measures including providing baseline data for parameterising infectious disease mathematical models including those assessing the impact of clinical interventions such as pneumococcal conjugate vaccines.
| S-EPMC7820366 | biostudies-literature
Project description:BackgroundIt is widely accepted that people living with diabetes (PLWD) are at increased risk of infectious disease, yet there is a paucity of epidemiology studies on the relationship between diabetes and infectious disease in SSA. In a region with a high burden of infectious disease, this has serious consequences for PLWD.Methods and findingsUsing routinely collected longitudinal health data, we describe the epidemiology of diabetes in a large virtual cohort of PLWD who have a high burden of HIV and TB, from the Khayelitsha subdistrict in the Western Cape Province in South Africa. We described the relationship between previous TB, newly diagnosed TB disease and HIV infection on diabetes using HbA1c results as an outcome measure. The study population was predominately female (67%), 13% had a history of active TB disease and 18% were HIV positive. The HIV positive group had diabetes ascertained at a significantly younger age (46 years c.f. 53 years respectively, p<0.001) and in general had increased HbA1c values over time after their HIV diagnosis, when compared to the HIV-negative group. There was no evidence of TB disease influencing the trajectory of glycaemic control in the long term, but diabetes patients who developed active TB had higher mortality than those without TB (12.4% vs 6.7% p-value < 0.001). HIV and diabetes are both chronic diseases whose long-term management includes drug therapy, however, only 52.8% of the study population with an HIV-diabetes comorbidity had a record of diabetes treatment. In addition, the data suggest overall poor glycaemic control in the study population with only 24.5% of the participants having an HbA1c <7% at baseline despite 85% of the study population being on diabetes treatment.ConclusionThe epidemiologic findings in this exploratory study highlight the need for further research into diabetes outcomes in a high TB and HIV burden setting and demonstrate that routine health data are a valuable resource for understanding disease epidemiology in the general population.
| S-EPMC8104376 | biostudies-literature
Project description:BackgroundSecond-line antiretroviral therapy (ART) based on ritonavir-boosted protease inhibitors (bPIs) represents the only available option after first-line failure for the majority of individuals living with human immunodeficiency virus (HIV) worldwide. Maximizing their effectiveness is imperative.MethodsThis cohort study was nested within the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa. We prospectively investigated risk factors for virological failure (VF) of bPI-based ART in the combined study arms. VF was defined by a plasma viral load >1000 copies/mL ≥6 months after initiating bPI-based ART. Cumulative incidence of VF was estimated and competing risk regression was used to derive the subdistribution hazard ratio (SHR) of the associations between VF and patient clinical and demographic factors, taking into account death and loss to follow-up.ResultsOne hundred one participants contributed 178.7 person-years of follow-up. Sixty-five percent were female; the median age was 37.4 years. Second-line ART regimens were based on ritonavir-boosted lopinavir, combined with zidovudine or tenofovir plus lamivudine or emtricitabine. The incidence of VF on second-line ART was 12.9 per 100 person-years (n = 23), and prevalence of VF at censoring was 17.8%. Thirteen of these 23 (56.5%) virologic failures resuppressed after a median of 8.0 months (interquartile range, 2.8-16.8 months) in this setting where viral load monitoring was available. Tuberculosis treatment was associated with VF (SHR, 11.50 [95% confidence interval, 3.92-33.74]; P < .001).ConclusionsSecond-line VF was frequent in this setting. Resuppression occurred in more than half of failures, highlighting the value of viral load monitoring of second-line ART. Tuberculosis was associated with VF; therefore, novel approaches to optimize the effectiveness of PI-based ART in high-tuberculosis-burden settings are needed.Clinical trials registrationNCT01509508.
| S-EPMC5439490 | biostudies-literature
Project description:BackgroundIn utero exposure to human immunodeficiency virus (HIV) and antiretroviral (ART) is associated with adverse birth outcomes, which are often attributed to alterations in placental morphology. This study used structural equation models (SEMs) to examine the impact of HIV and ART exposure on fetal growth outcomes and whether these associations are mediated by placental morphology in urban-dwelling Black South African women.MethodsThis prospective cohort study included pregnant women living with HIV (WLWH, n = 122) and not living with HIV (WNLWH, n = 250) that underwent repeated ultrasonography during pregnancy, and at delivery, to determine fetal growth parameters in Soweto, South Africa. The size and the velocity of fetal growth measures (i.e., head and abdominal circumference, biparietal diameter, and femur length) were calculated using the Superimposition by Translation and Rotation. Placenta digital photographs taken at delivery were used to estimate morphometric parameters and trimmed placental weight was measured. All WLWH were receiving ART for the prevention of vertical transmission of HIV.ResultsA trend towards a lower placental weight and significantly shorter umbilical cord length was reported in WLWH compared to their counterparts. After sex stratification, umbilical cord length was significantly shorter in males born to WLWH than in male fetuses born to WNLWH (27.3 (21.6-32.8) vs. 31.4 (25.0-37.0) cm, p = 0.015). In contrast, female fetuses born to WLWH had lower placental weight, birth weight (2.9 (2.3-3.1) vs. 3.0 (2.7-3.2) kg), and head circumference (33 (32-34) vs. 34 (33-35) cm) than their counterparts (all p ≤ 0.05). The SEM models showed an inverse association between HIV and head circumference size and velocity in female fetuses. In contrast, HIV and ART exposure was positively associated with femur length growth (both size and velocity) and abdominal circumference velocity in male fetuses. None of these associations appeared to be mediated via placental morphology.ConclusionOur findings suggest that HIV and ART exposure directly affects head circumference growth in females and abdominal circumference velocity in male fetuses; but may improve femur length growth in male fetuses only.
| S-EPMC10239583 | biostudies-literature
Project description:Introduction Because cerebrospinal fluid (CSF) samples are difficult to obtain for paediatric HIV, few studies have attempted to profile neurometabolic dysregulation.Aim and objectiveThe aim of this exploratory study was to profile the neurometabolic state of CSF from a South African paediatric cohort using GCxGC-TOF/MS. The study included 54 paediatric cases (< 12 years), 42 HIV-negative controls and 12 HIV-positive individuals.ResultsThe results revealed distinct metabolic alterations in the HIV-infected cohort. In the PLS-DA model, 18 metabolites significantly discriminated between HIV-infected and control groups. In addition, fold-change analysis, Mann-Whitney U tests, and effect size measurements verified these findings. Notably, lactose, myo-inositol, and glycerol, although not significant by p-value alone, demonstrated practical significance based on the effect size.ConclusionsThis study provided valuable insights on the impact of HIV on metabolic pathways, including damage to the gut and blood-brain barrier, disruption of bioenergetics processes, gliosis, and a potential marker for antiretroviral therapy. Nevertheless, the study recognized certain constraints, notably a limited sample size and the absence of a validation cohort. Despite these limitations, the rarity of the study's focus on paediatric HIV research underscores the significance and unique contributions of its findings.
| S-EPMC10907482 | biostudies-literature