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Impact of Intermediate Hyperglycemia and Diabetes on Immune Dysfunction in Tuberculosis
Supplementary Data:
Supplementary materials are available at Clinical Infectious Diseases online at https://academic.oup.com/cid/article/72/1/69/5857148#274319223 . Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.Copyright © The Author(s) 2020. Background:
People with diabetes have an increased risk of developing active tuberculosis (TB) and are more likely to have poor TB-treatment outcomes, which may impact on control of TB as the prevalence of diabetes is increasing worldwide. Blood transcriptomes are altered in patients with active TB relative to healthy individuals. The effects of diabetes and intermediate hyperglycemia (IH) on this transcriptomic signature were investigated to enhance understanding of immunological susceptibility in diabetes-TB comorbidity.
Methods:
Whole blood samples were collected from active TB patients with diabetes (glycated hemoglobin [HbA1c] ≥6.5%) or IH (HbA1c = 5.7% to <6.5%), TB-only patients, and healthy controls in 4 countries: South Africa, Romania, Indonesia, and Peru. Differential blood gene expression was determined by RNA-seq (n = 249).
Results:
Diabetes increased the magnitude of gene expression change in the host transcriptome in TB, notably showing an increase in genes associated with innate inflammatory and decrease in adaptive immune responses. Strikingly, patients with IH and TB exhibited blood transcriptomes much more similar to patients with diabetes-TB than to patients with only TB. Both diabetes-TB and IH-TB patients had a decreased type I interferon response relative to TB-only patients.
Conclusions:
Comorbidity in individuals with both TB and diabetes is associated with altered transcriptomes, with an expected enhanced inflammation in the presence of both conditions, but also reduced type I interferon responses in comorbid patients, suggesting an unexpected uncoupling of the TB transcriptome phenotype. These immunological dysfunctions are also present in individuals with IH, showing that altered immunity to TB may also be present in this group. The TB disease outcomes in individuals with IH diagnosed with TB should be investigated further.European Union’s Seventh Framework Programme (FP7 2007-2013 - Health) under grant agreement No 305279
Point of care HbA1c level for diabetes mellitus management and its accuracy among tuberculosis patients: a study in four countries
BACKGROUND: Diabetes mellitus (DM) is common among tuberculosis (TB) patients and often undiagnosed or poorly controlled. We compared point of care (POC) with laboratory glycated haemoglobin (HbA1c) testing among newly diagnosed TB patients to assess POC test accuracy, safety and acceptability in settings in which immediate access to DM services may be difficult.
METHODS: We measured POC and accredited laboratory HbA1c (using high-performance liquid chromatography) in 1942 TB patients aged 18 years recruited from Peru, Romania, Indonesia and South Africa. We calculated overall agreement and individual variation (mean ± 2 standard deviations) stratified by country, age, sex, body mass index (BMI), HbA1c level and comorbidities (anaemia, human immunodeficiency virus [HIV]). We used an error grid approach to identify disagreement that could raise significant concerns.
RESULTS: Overall mean POC HbA1c values were modestly higher than laboratory HbA1c levels by 0.1% units (95%CI 0.1–0.2); however, there was a substantial discrepancy for those with severe anaemia (1.1% HbA1c, 95%CI 0.7–1.5). For 89.6% of 1942 patients, both values indicated the same DM status (no DM, HbA1c <6.5%) or had acceptable deviation (relative difference <6%). Individual agreement was variable, with POC values up to 1.8% units higher or 1.6% lower. For a minority, use of POC HbA1c alone could result in error leading to potential overtreatment (n = 40, 2.1%) or undertreatment (n = 1, 0.1%). The remainder had moderate disagreement, which was less likely to influence clinical decisions.
CONCLUSION: POC HbA1c is pragmatic and sufficiently accurate to screen for hyperglycaemia and DM risk among TB patients
The ASOS Surgical Risk Calculator: development and validation of a tool for identifying African surgical patients at risk of severe postoperative complications
Background:
The African Surgical Outcomes Study (ASOS) showed that surgical patients in Africa have a mortality twice the global average. Existing risk assessment tools are not valid for use in this population because the pattern of risk for poor outcomes differs from high-income countries. The objective of this study was to derive and validate a simple, preoperative risk stratification tool to identify African surgical patients at risk for in-hospital postoperative mortality and severe complications.
Methods:
ASOS was a 7-day prospective cohort study of adult patients undergoing surgery in Africa. The ASOS Surgical Risk Calculator was constructed with a multivariable logistic regression model for the outcome of in-hospital mortality and severe postoperative complications. The following preoperative risk factors were entered into the model; age, sex, smoking status, ASA physical status, preoperative chronic comorbid conditions, indication for surgery, urgency, severity, and type of surgery.
Results:
The model was derived from 8799 patients from 168 African hospitals. The composite outcome of severe postoperative complications and death occurred in 423/8799 (4.8%) patients. The ASOS Surgical Risk Calculator includes the following risk factors: age, ASA physical status, indication for surgery, urgency, severity, and type of surgery. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.805 and good calibration with c-statistic corrected for optimism of 0.784.
Conclusions:
This simple preoperative risk calculator could be used to identify high-risk surgical patients in African hospitals and facilitate increased postoperative surveillance.
© 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.Medical Research Council of South Africa gran
Maternal and neonatal outcomes after caesarean delivery in the African Surgical Outcomes Study: a 7-day prospective observational cohort study.
BACKGROUND: Maternal and neonatal mortality is high in Africa, but few large, prospective studies have been done to investigate the risk factors associated with these poor maternal and neonatal outcomes. METHODS: A 7-day, international, prospective, observational cohort study was done in patients having caesarean delivery in 183 hospitals across 22 countries in Africa. The inclusion criteria were all consecutive patients (aged ≥18 years) admitted to participating centres having elective and non-elective caesarean delivery during the 7-day study cohort period. To ensure a representative sample, each hospital had to provide data for 90% of the eligible patients during the recruitment week. The primary outcome was in-hospital maternal mortality and complications, which were assessed by local investigators. The study was registered on the South African National Health Research Database, number KZ_2015RP7_22, and on ClinicalTrials.gov, number NCT03044899. FINDINGS: Between February, 2016, and May, 2016, 3792 patients were recruited from hospitals across Africa. 3685 were included in the postoperative complications analysis (107 missing data) and 3684 were included in the maternal mortality analysis (108 missing data). These hospitals had a combined number of specialist surgeons, obstetricians, and anaesthetists totalling 0·7 per 100 000 population (IQR 0·2-2·0). Maternal mortality was 20 (0·5%) of 3684 patients (95% CI 0·3-0·8). Complications occurred in 633 (17·4%) of 3636 mothers (16·2-18·6), which were predominantly severe intraoperative and postoperative bleeding (136 [3·8%] of 3612 mothers). Maternal mortality was independently associated with a preoperative presentation of placenta praevia, placental abruption, ruptured uterus, antepartum haemorrhage (odds ratio 4·47 [95% CI 1·46-13·65]), and perioperative severe obstetric haemorrhage (5·87 [1·99-17·34]) or anaesthesia complications (11·47 (1·20-109·20]). Neonatal mortality was 153 (4·4%) of 3506 infants (95% CI 3·7-5·0). INTERPRETATION: Maternal mortality after caesarean delivery in Africa is 50 times higher than that of high-income countries and is driven by peripartum haemorrhage and anaesthesia complications. Neonatal mortality is double the global average. Early identification and appropriate management of mothers at risk of peripartum haemorrhage might improve maternal and neonatal outcomes in Africa. FUNDING: Medical Research Council of South Africa.Medical Research Council of South Africa