Comparing tuberculosis gene signatures in malnourished individuals using the TBSignatureProfiler.

BACKGROUND: Gene expression signatures have been used as biomarkers of tuberculosis (TB) risk and outcomes. Platforms are needed to simplify access to these signatures and determine their validity in the setting of comorbidities. We developed a computational profiling platform of TB signature gene sets and characterized the diagnostic ability of existing signature gene sets to differentiate active TB from LTBI in the setting of malnutrition. METHODS: We curated 45 existing TB-related signature gene sets and developed our TBSignatureProfiler software toolkit that estimates gene set activity using multiple enrichment methods and allows visualization of single- and multi-pathway results. The TBSignatureProfiler software is available through Bioconductor and on GitHub. For evaluation in malnutrition, we used whole blood gene expression profiling from 23 severely malnourished Indian individuals with TB and 15 severely malnourished household contacts with latent TB infection (LTBI). Severe malnutrition was defined as body mass index (BMI) < 16 kg/m2 in adults and based on weight-for-height Z scores in children < 18 years. Gene expression was measured using RNA-sequencing. RESULTS: The comparison and visualization functions from the TBSignatureProfiler showed that TB gene sets performed well in malnourished individuals; 40 gene sets had statistically significant discriminative power for differentiating TB from LTBI, with area under the curve ranging from 0.662-0.989. Three gene sets were not significantly predictive. CONCLUSION: Our TBSignatureProfiler is a highly effective and user-friendly platform for applying and comparing published TB signature gene sets. Using this platform, we found that existing gene sets for TB function effectively in the setting of malnutrition, although differences in gene set applicability exist. RNA-sequencing gene sets should consider comorbidities and potential effects on diagnostic performance.

Typical Diagnostic Reference Levels of Common Indications for Computed Tomography Scans Among Adult Patients in Uganda: a Cross-sectional Study.

Background: Medical exposure to ionizing radiation has increased due to an increase in the number of computerized tomography (CT) scan examinations performed. The International Commission on Radiological Protection (ICRP) recommends indication-based diagnostic reference levels (IB-DRLs) as an effective tool that aids in optimizing CT scan radiation doses. In many low-income settings, there is a lack of IB-DRLs to support optimization of radiation doses. Objective: To establish typical DRLs for common CT scan indications among adult patients in Kampala, Uganda. Methodology: A cross sectional study design was employed involving 337 participants enrolled from three hospitals using systematic sampling. The participants were adults who had been referred for a CT scan. The typical DRL of each indication was determined as the median value of the pooled distribution of CTDIvol (mGy) data and the median value of the pooled distribution of total DLP (tDLP)(mGy.cm) data from three hospitals. Comparison was made to anatomical, and indication based DRLs from other studies. Results: 54.3% of the participants were male. The following were typical DRLs for: acute stroke (30.17mGy and 653mGy.cm); head trauma (32.04mGy and 878mGy.cm); interstitial lung diseases/ high resolution chest CT scan (4.66mGy and 161mGy.cm); pulmonary embolism (5.03mGy and 273mGy.cm); abdominopelvic lesion (6.93mGy and 838mGy.cm) and urinary calculi (7.61mGy and 975mGy.cm). Indication based total Dose Length Product (tDLP) DRLs was lower than tDLP DRLs of a whole anatomical region by 36.4% on average. Most of the developed typical IB-DLP DRLs were lower or comparable to values from studies in Ghana and Egypt in all indications besides urinary calculi while they were higher than values in a French study in all indications besides acute stroke and head trauma. Conclusion: Typical IB-DRLs is a good clinical practice tool for optimization of CT doses and therefore recommended for use to manage CT radiation dose. The developed IB-DRLs varied from international values due to differences in selection of CT scan parameters and standardization of CT imaging protocols may narrow the variation. This study can serve as baseline for establishment of national indication-based CT DRLs in Uganda.

Mycobacterium tuberculosis disease associates with higher HIV-1-specific antibody responses.

Mycobacterium tuberculosis (Mtb) is the most common infection among people with HIV (PWH). Mtb disease-associated inflammation could affect HIV-directed immune responses in PWH. We show that HIV antibodies are broader and more potent in PWH in the presence as compared to the absence of Mtb disease. With co-existing Mtb disease, the virus in PWH also encounters unique antibody selection pressure. The Mtb-linked HIV antibody enhancement associates with specific mediators important for B cell and antibody development. This Mtb humoral augmentation does not occur due to cross-reactivity, a generalized increase in all antibodies, or differences in duration or amount of antigen exposure. We speculate that the co-localization of Mtb and HIV in lymphatic tissues leads to the emergence of potent HIV antibodies. PWH's Mtb disease status has implications for the future use of HIV broadly neutralizing antibodies as prophylaxis or treatment and the induction of better humoral immunity.

Non-surgical oral hygiene interventions on disease activity of Rheumatoid arthritis patients with periodontitis: A randomized controlled trial.

Background. Periodontitis and rheumatoid arthritis have similar epidemiology and pathophysiology. Understanding the interaction between these two diseases is vital in our settings. We set out to assess the effect of oral hygiene interventions on disease activity of rheumatoid arthritis patients with periodontitis in Kampala, Uganda. Methods. Fifty-eight patients attending an arthritis clinic with rheumatoid arthritis and periodontitis were randomly assigned to either an intervention group or a control group. Patients diagnosed with rheumatoid arthritis at least two years before, who were on the same medication, dose, or formulation for RA treatment during the preceding three months, were included. The patients were >18 years of age, would be available for all the study visits in the next six months, had at least six natural teeth, had periodontal disease classified as Dutch Periodontal Index (DPSI) >3 and provided written informed consent. Those who had a chronic disorder requiring chronic or intermittent use of antibiotics, were pregnant, were lactating, or had intent to become pregnant were excluded. The primary outcome measure was a change in Disease Activity Score of 28 Joints (DAS28 score) in two 3-month follow-up periods after the intervention. The secondary outcome measure was a change in periodontal status. Results. There was a statistically significant improvement in the DAS-28 score in both the intervention and control arms during the follow-up period (P<0.01). The participants carrying more than one bacterial species had worse DAS-28 scores. Conclusion. Oral hygiene interventions given to RA patients could drastically improve their RA treatment outcomes, especially in resource-limited settings.

Periodontitis and Rheumatoid Arthritis in sub-Saharan Africa, gaps and way forward: a systematic review and meta-analysis.

BACKGROUND: This review identified papers that described periodontitis and rheumatoid arthritis in sub-Saharan Africa. Only English language publications from January 2010 to December 2017 describing original research in sub-Saharan Africa on the association between periodontitis and rheumatoid arthritis were considered for this study. METHODS: Published databases: PubMed, Science direct and Google scholar, were searched using terms "periodontitis", "rheumatoid arthritis" and "Sub-Saharan Africa" to generate a set of putative studies. Articles with data on both rheumatoid arthritis and periodontitis compared to controls were selected. Studies on the association of periodontitis with cardiovascular disease, arthritis or rheumatoid arthritis alone were excluded. Data were extracted, critically appraised, and analyzed using a random-effect Mantel-Haenszel meta-analysis on plaque index, gingival index, pocket depth and clinical attachment loss. RESULTS: Three publications were selected for the systematic review and 2 for the meta-analysis. Two studies were from Sudan, and one was from Burina Faso. There was a significant increase in pocket depth (mean difference: 0.31; 95% CI: 0.21, 0.41; N= 274; (p ≤ 0.001) and clinical attachment loss (mean difference: 0.47; 95% CI: 0.22, 0.75; N= 274; (p ≤ 0.001) in participants with rheumatoid arthritis compared to normal controls. CONCLUSION: Findings from these combined studies show a significant relationship between periodontal disease and rheumatoid arthritis with increased periodontal pocket depth and clinical attachment loss. They also highlight the need for additional work especially in the area of associating rheumatoid arthritis with P. gingivalis, the oral microbiome and treating periodontal diseases to help in the management of rheumatoid arthritis.