Oral Swab Specimens Tested With Xpert MTB/RIF Ultra Assay for Diagnosis of Pulmonary Tuberculosis in Children: A Diagnostic Accuracy Study.

BACKGROUND: Microbiologic diagnosis of childhood tuberculosis may be difficult. Oral swab specimens are a potential noninvasive alternative to sputum specimens for diagnosis. METHODS: This was a prospective diagnostic accuracy study of oral swab specimens (buccal and tongue) for pulmonary tuberculosis diagnosis in children (aged ≤ 15 years) in 2 South African hospital sites. Children with cough of any duration as well as a positive tuberculin skin test result, tuberculosis contact, loss of weight, or chest radiograph suggestive of pulmonary tuberculosis were enrolled. Two induced sputum specimens were tested with Xpert MTB/RIF (or Xpert MTB/RIF Ultra) assay and liquid culture. Oral swab specimens were obtained before sputum specimens, frozen, and later tested with Xpert MTB/RIF Ultra. Children were classified as microbiologically confirmed tuberculosis, unconfirmed tuberculosis (receipt of tuberculosis treatment), or unlikely tuberculosis according to National Institutes of Health consensus definitions based on sputum microbiologic results. RESULTS: Among 291 participants (median age [interquartile range], 32 [14-73] months), 57 (20%) had human immunodeficiency virus (HIV), and 87 (30%) were malnourished; 90 (31%) had confirmed pulmonary tuberculosis (rifampicin resistant in 6 [7%] ), 157 (54%), unconfirmed pulmonary tuberculosis, and 44 (15%), unlikely tuberculosis. A single oral swab specimen was obtained from 126 (43%) of the participants (tongue in 96 and buccal in 30) and 2 swab specimens from 165 (57%) (tongue in 110 and buccal in 55). Sensitivity was low (22% [95% confidence interval, 15%-32%]) for all swab specimens combined (with confirmed pulmonary tuberculosis as reference), but specificity was high (100% [91%-100%]). The highest sensitivity was 33% (95% confidence interval, 15%-58%) among participants with HIV. The overall yield was 6.9% with 1 oral swab specimen and 7.2% with 2. CONCLUSIONS: Use of the Xpert MTB/RIF Ultra assay with oral swab specimens provides poor yield for microbiologic pulmonary tuberculosis confirmation in children.

The nasopharyngeal microbiome in South African children with lower respiratory tract infection: a nested case-control study of the Drakenstein Child Health Study.

Background: Lower respiratory tract infection (LRTI) is a leading cause of infant morbidity and mortality globally. LRTI may be caused by viral or bacterial infections, individually or in combination. We investigated associations between LRTI and infant nasopharyngeal (NP) viruses and bacteria in a South African birth cohort. Methods: In a case-control study of infants enrolled in the Drakenstein Child Health Study (DCHS), LRTI cases were identified prospectively and age-matched with controls from the cohort. NP swabs were tested using quantitative real-time polymerase chain reaction (qPCR) and 16S rRNA gene amplicon sequencing. We calculated adjusted Conditional Odds Ratios (aORs) for qPCR targets and used mixed effects models to identify differentially abundant taxa between LRTI cases and controls and explore viral-bacterial interactions. Results: Respiratory Syncytial Virus (RSV) [aOR: 5.69, 95% CI: 3.03-10.69], human rhinovirus (HRV) [1.47, 1.03-2.09], parainfluenza virus [3.46, 1.64-7.26], adenovirus [1.99, 1.08-3.68], enterovirus [2.32, 1.20-4.46], Haemophilus influenzae [1.72, 1.25-2.37], Klebsiella pneumoniae [2.66, 1.59-4.46], or high-density (> 6.9 log10 copies/mL) Streptococcus pneumoniae [1.53, 1.01-2.32] were associated with LRTI. Using 16S sequencing, LRTI was associated with increased relative abundance of Haemophilus (q = 0.0003) and decreased relative abundance of Dolosigranulum (q = 0.001), Corynebacterium (q = 0.091) and Neisseria (q = 0.004). In samples positive for RSV, Staphylococcus and Alloprevotella were present at lower relative abundance in cases than controls. In samples positive for parainfluenza virus or HRV, Haemophilus was present at higher relative abundance in cases. Conclusions: The associations between bacterial taxa and LRTI are strikingly similar to those identified in high-income countries, suggesting a conserved phenotype. RSV was the major virus associated with LRTI. H. influenzae appears to be the major bacterial driver of LRTI, acting synergistically with viruses. The Gram-positive bacteria Dolosigranulum and Corynebacteria may protect against LRTI, while Staphylococcus was associated with reduced risk of RSV-related LRTI. Funding: National Institutes of Health of the USA, Bill and Melinda Gates Foundation, National Research Foundation South Africa, South African Medical Research Council, L'Oréal-UNESCO For Women in Science South Africa, Australian National Health and Medical Research Council.

Decoding the Gut Microbiota-Gestational Diabetes Link: Insights from the Last Seven Years.

The human microbiome, a complex ecosystem of bacteria, viruses, and protozoans living in symbiosis with the host, plays a crucial role in human health, influencing everything from metabolism to immune function. Dysbiosis, or an imbalance in this ecosystem, has been linked to various health issues, including diabetes and gestational diabetes (GD). In diabetes, dysbiosis affects the function of adipose tissue, leading to the release of adipokines and cytokines, which increase inflammation and insulin resistance. During pregnancy, changes to the microbiome can exacerbate glucose intolerance, a common feature of GD. Over the past years, burgeoning insights into the gut microbiota have unveiled its pivotal role in human health. This article comprehensively reviews literature from the last seven years, highlighting the association between gut microbiota dysbiosis and GD, as well as the metabolism of antidiabetic drugs and the potential influences of diet and probiotics. The underlying pathophysiological mechanisms discussed include the impact of dysbiosis on systemic inflammation and the interplay with genetic and environmental factors. By focusing on recent studies, the importance of considering microbial health in the prevention and treatment of GD is emphasized, providing insights into future research directions and clinical applications to improve maternal-infant health outcomes.

Empagliflozin and Dapagliflozin Improve Endothelial Function in Mexican Patients with Type 2 Diabetes Mellitus: A Double-Blind Clinical Trial.

AIM: To assess the acute effect of empagliflozin versus dapagliflozin administration on flow-mediated vasodilation in patients with type 2 diabetes mellitus. DESIGN: A double-blind clinical trial, at the Experimental and Clinical Therapeutics Institute, University Health Sciences Center, at the Universidad de Guadalajara, in inpatients with T2D according to the 2023 ADA criteria. METHODS: Thirty patients (15 males and 15 females), aged between 35 and 65 years, were included in this study, according to the 2023 ADA criteria. The eligible patients were randomly assigned to three groups: empagliflozin 25 mg once daily, dapagliflozin 10 mg once daily, or placebo once daily. Anthropometric parameters were taken using validated techniques. FMD was measured using a high-resolution semiautomatic ultrasound UNEX-EF 38G (UNEX Co., Ltd., Nagoya, Japan). Arterial tension was determined with the OMRON electronic digital sphygmomanometer (HEM 907 XL, Kyoto, Japan). RESULTS: The group of patients who received empagliflozin had a significantly lower baseline flow-mediated dilation (FMD) compared to the group receiving dapagliflozin (p = 0.017); at the end of this study, the empagliflozin group achieved a comparable FMD to the dapagliflozin group (p = 0.88). CONCLUSION: After the treatment period, the empagliflozin and dapagliflozin groups achieved similar FMD, suggesting a class effect.

Comparison of a Real-Time Multiplex PCR and Sequetyping Assay for Pneumococcal Serotyping.

BACKGROUND: Pneumococcal serotype identification is essential to monitor pneumococcal vaccine effectiveness and serotype replacement. Serotyping by conventional serological methods are costly, labour-intensive, and require significant technical expertise. We compared two different molecular methods to serotype pneumococci isolated from the nasopharynx of South African infants participating in a birth cohort study, the Drakenstein Child Health Study, in an area with high 13-valent pneumococcal conjugate vaccine (PCV13) coverage. METHODS: A real-time multiplex PCR (rmPCR) assay detecting 21 different serotypes/-groups and a sequetyping assay, based on the sequence of the wzh gene within the pneumococcal capsular locus, were compared. Forty pneumococcal control isolates, with serotypes determined by the Quellung reaction, were tested. In addition, 135 pneumococcal isolates obtained from the nasopharynx of healthy children were tested by both serotyping assays and confirmed by Quellung testing. Discordant results were further investigated by whole genome sequencing of four isolates. RESULTS: Of the 40 control isolates tested, 25 had a serotype covered by the rmPCR assay. These were all correctly serotyped/-grouped. Sequetyping PCR failed in 7/40 (18%) isolates. For the remaining isolates, sequetyping assigned the correct serotype/-group to 29/33 (88%) control isolates. Of the 132/135 (98%) nasopharyngeal pneumococcal isolates that could be typed, 69/132 (52%) and 112/132 (85%) were assigned the correct serotype/-group by rmPCR and sequetyping respectively. The serotypes of 63/132 (48%) isolates were not included in the rmPCR panel. All except three isolates (serotype 25A and 38) were theoretically amplified and differentiated into the correct serotype/-group with some strains giving ambigous results (serotype 13/20, 17F/33C, and 11A/D/1818F). Of the pneumococcal serotypes detected in this study, 69/91 (76%) were not included in the current PCV13. The most frequently identified serotypes were 11A, 13, 15B/15C, 16F and 10A. CONCLUSION: The rmPCR assay performed well for the 21 serotypes/-groups included in the assay. However, in our study setting, a large proportion of serotypes were not detected by rmPCR. The sequetyping assay performed well, but did misassign specific serotypes. It may be useful for regions where vaccine serotypes are less common, however confirmatory testing is advisable.