Source-tracking ESBL-producing bacteria at the maternity ward of Mulago hospital, Uganda:ESBL-producing bacteria at the maternity ward of Mulago Hospital, Uganda

IntroductionEscherichia coli, Klebsiella pneumoniae and Enterobacter (EKE) are the leading cause of mortality and morbidity in neonates in Africa. The management of EKE infections remains challenging given the global emergence of carbapenem resistance in Gram-negative bacteria. This study aimed to investigate the source of EKE organisms for neonates in the maternity environment of a national referral hospital in Uganda, by examining the phenotypic and molecular characteristics of isolates from mothers, neonates, and maternity ward.MethodsFrom August 2015 to August 2016, we conducted a cross-sectional study of pregnant women admitted for elective surgical delivery at Mulago hospital in Kampala, Uganda; we sampled (nose, armpit, groin) 137 pregnant women and their newborns (n = 137), as well as health workers (n = 67) and inanimate objects (n = 70 -beds, ventilator tubes, sinks, toilets, door-handles) in the maternity ward. Samples (swabs) were cultured for growth of EKE bacteria and isolates phenotypically/molecularly investigated for antibiotic sensitivity, as well as β-lactamase and carbapenemase activity. To infer relationships among the EKE isolates, spatial cluster analysis of phenotypic and genotypic susceptibility characteristics was done using the Ridom server.ResultsGram-negative bacteria were isolated from 21 mothers (15%), 15 neonates (11%), 2 health workers (3%), and 13 inanimate objects (19%); a total of 131 Gram-negative isolates were identified of which 104 were EKE bacteria i.e., 23 (22%) E. coli, 50 (48%) K. pneumoniae, and 31 (30%) Enterobacter. Carbapenems were the most effective antibiotics as 89% (93/104) of the isolates were susceptible to meropenem; however, multidrug resistance was prevalent i.e., 61% (63/104). Furthermore, carbapenemase production and carbapenemase gene prevalence were low; 10% (10/104) and 6% (6/104), respectively. Extended spectrum β-lactamase (ESBL) production occurred in 37 (36%) isolates though 61 (59%) carried ESBL-encoding genes, mainly blaCTX-M (93%, 57/61) implying that blaCTX-M is the ideal gene for tracking ESBL-mediated resistance at Mulago. Additionally, spatial cluster analysis revealed isolates from mothers, new-borns, health workers, and environment with similar phenotypic/genotypic characteristics, suggesting transmission of multidrug-resistant EKE to new-borns.ConclusionOur study shows evidence of transmission of drug resistant EKE bacteria in the maternity ward of Mulago hospital, and the dynamics in the ward are more likely to be responsible for transmission but not individual mother characteristics. The high prevalence of drug resistance genes highlights the need for more effective infection prevention/control measures and antimicrobial stewardship programs to reduce spread of drug-resistant bacteria in the hospital, and improve patient outcomes

Type 2 Diabetes Mellitus and Latent Tuberculosis Infection Moderately Influence Innate Lymphoid Cell Immune Responses in Uganda

Background: Type 2 diabetes mellitus (T2DM) is a major risk factor for the acquisition of latent tuberculosis (TB) infection (LTBI) and development of active tuberculosis (ATB), although the immunological basis for this susceptibility remains poorly characterised. Innate lymphoid cells (ILCs) immune responses to TB infection in T2DM comorbidity is anticipated to be reduced. We compared ILC responses (frequency and cytokine production) among adult patients with LTBI and T2DM to patients (13) with LTBI only (14), T2DM only (10) and healthy controls (11). Methods: Using flow cytometry, ILC phenotypes were categorised based on (Lin-CD127+CD161+) markers into three types: ILC1 (Lin-CD127+CD161+CRTH2-CD117-); ILC2 (Lin-CD127+CD161+CRTH2+) and ILC3 (Lin-CD127+CD161+CRTH2-NKp44+/-CD117+). ILC responses were determined using cytokine production by measuring percentage expression of interferon-gamma (IFN-γ) for ILC1, interleukin (IL)-13 for ILC2, and IL-22 for ILC3. Glycaemic control among T2DM patients was measured using glycated haemoglobin (HbA1c) levels. Data were analysed using FlowJo version 10.7.1, and GraphPad Prism version 8.3. Results: Compared to healthy controls, patients with LTBI and T2DM had reduced frequencies of ILC2 and ILC3 respectively (median (IQR): 0.01 (0.005-0.04) and 0.002 (IQR; 0.002-0.007) and not ILC1 (0.04 (0.02-0.09) as expected. They also had increased production of IFN-γ [median (IQR): 17.1 (5.6-24.9)], but decreased production of IL-13 [19.6 (12.3-35.1)]. We however found that patients with T2DM had lower ILC cytokine responses in general but more marked for IL-22 production (median (IQR): IFN-γ 9.3 (4.8-22.6); IL-13 22.2 (14.7-39.7); IL-22 0.7 (IQR; 0.1-2.1) p-value 0.02), which highlights the immune suppression status of T2DM. We also found that poor glycaemic control altered ILC immune responses. Conclusion: This study demonstrates that LTBI and T2DM, and T2DM were associated with slight alterations of ILC immune responses. Poor T2DM control also slightly altered these ILC immune responses. Further studies are required to assess if these responses recover after treatment of either TB or T2DM

The effect of biomass smoke exposure on quality-of-life among Ugandan patients treated for tuberculosis: A cross-sectional analysis.

More than half the global population burns biomass fuels for cooking and home heating, especially in low-middle income countries. This practice is a prominent source of indoor air pollution and has been linked to the development of a variety of cardiopulmonary diseases, including Tuberculosis (TB). The purpose of this cross-sectional study was to investigate the association between current biomass smoke exposure and self-reported quality of life scores in a cohort of previous TB patients in Uganda. We reviewed medical records from six TB clinics from 9/2019-9/2020 and conducted phone interviews to obtain information about biomass smoke exposure. A random sample of these patients were asked to complete three validated quality-of-life surveys including the St. Georges Respiratory Questionnaire (SGRQ), the EuroQol 5 Dimension 3 Level system (EQ-5D-3L) which includes the EuroQol Visual Analog Scale (EQ-VAS), and the Patient Health Questionnaire 9 (PHQ-9). The cohort was divided up into 3 levels based on years of smoke exposure-no-reported smoke exposure (0 years), light exposure (1-19 years), and heavy exposure (20+ years), and independent-samples-Kruskal-Wallis testing was performed with post-hoc pairwise comparison and the Bonferroni correction. The results of this testing indicated significant increases in survey scores for patients with current biomass exposure and a heavy smoke exposure history (20+ years) compared to no reported smoke exposure in the SGRQ activity scores (adj. p = 0.018) and EQ-5D-3L usual activity scores (adj. p = 0.002), indicating worse activity related symptoms. There was a decrease in EQ-VAS scores for heavy (adj. p = 0.007) and light (adj. p = 0.017) exposure groups compared to no reported exposure, indicating lower perceptions of overall health. These results may suggest worse outcomes or baseline health for TB patients exposed to biomass smoke at the time of treatment and recovery, however further research is needed to characterize the effect of indoor air pollution on TB treatment outcomes

De-identified data.

More than half the global population burns biomass fuels for cooking and home heating, especially in low-middle income countries. This practice is a prominent source of indoor air pollution and has been linked to the development of a variety of cardiopulmonary diseases, including Tuberculosis (TB). The purpose of this cross-sectional study was to investigate the association between current biomass smoke exposure and self-reported quality of life scores in a cohort of previous TB patients in Uganda. We reviewed medical records from six TB clinics from 9/2019-9/2020 and conducted phone interviews to obtain information about biomass smoke exposure. A random sample of these patients were asked to complete three validated quality-of-life surveys including the St. Georges Respiratory Questionnaire (SGRQ), the EuroQol 5 Dimension 3 Level system (EQ-5D-3L) which includes the EuroQol Visual Analog Scale (EQ-VAS), and the Patient Health Questionnaire 9 (PHQ-9). The cohort was divided up into 3 levels based on years of smoke exposure–no-reported smoke exposure (0 years), light exposure (1–19 years), and heavy exposure (20+ years), and independent-samples-Kruskal-Wallis testing was performed with post-hoc pairwise comparison and the Bonferroni correction. The results of this testing indicated significant increases in survey scores for patients with current biomass exposure and a heavy smoke exposure history (20+ years) compared to no reported smoke exposure in the SGRQ activity scores (adj. p = 0.018) and EQ-5D-3L usual activity scores (adj. p = 0.002), indicating worse activity related symptoms. There was a decrease in EQ-VAS scores for heavy (adj. p = 0.007) and light (adj. p = 0.017) exposure groups compared to no reported exposure, indicating lower perceptions of overall health. These results may suggest worse outcomes or baseline health for TB patients exposed to biomass smoke at the time of treatment and recovery, however further research is needed to characterize the effect of indoor air pollution on TB treatment outcomes.</div

EuroQol Visual Analogue Scale (EQ6-VAS) scores in patients with heavy, light. and no-reported biomass smoke exposure.

Patients in heavy (SE = 8.533, p = 0.007) and light (SE = 9.123, p = 0.017) exposure groups had significantly lower scores compared to the no exposure group, indicating worse perception of their overall health.</p

Characteristics of all participants by exposure group.

Characteristics of all participants by exposure group.</p

Consort diagram summarizing data collection and exclusion.

SGRQ = St. George’s Respiratory Questionnaire, EQ-5D-3L = EuroQol-5D-3L, EQ-VAS = EuroQol Visual Analog Scale, PHQ9 = Patient Health Questionnaire. *A small number of subjects were able to finish at least one survey, but not all three due to time constraints, dropped calls, etc. The SGRQ has a significantly lower number of responses than the PHQ9 and EQ-5D-3L because it requires significantly longer time to complete, and some subjects had issues with time constraints.</p

Fig 2 -

(A) St. George Respiratory Questionnaire (SGRQ) activity scores in patients with heavy, light, and no-reported biomass smoke exposure. The heavy exposure group had significantly higher scores than the no reported exposure group (SE = 7.869 adj. p = 0.018), indicating greater activity limitations. (B) Distribution of scores on the EuroQol-SD-3L Usual Activities questionnaire between heavy, light, and no reported exposure groups. The heavy exposure group reported significantly higher scores than both the no reported exposure (SE = 6.208, adj. p = 0.002) and light exposure (SE = 7.906, adi. p = 0.041) groups, indicating more activity limitations.</p

Data key.

More than half the global population burns biomass fuels for cooking and home heating, especially in low-middle income countries. This practice is a prominent source of indoor air pollution and has been linked to the development of a variety of cardiopulmonary diseases, including Tuberculosis (TB). The purpose of this cross-sectional study was to investigate the association between current biomass smoke exposure and self-reported quality of life scores in a cohort of previous TB patients in Uganda. We reviewed medical records from six TB clinics from 9/2019-9/2020 and conducted phone interviews to obtain information about biomass smoke exposure. A random sample of these patients were asked to complete three validated quality-of-life surveys including the St. Georges Respiratory Questionnaire (SGRQ), the EuroQol 5 Dimension 3 Level system (EQ-5D-3L) which includes the EuroQol Visual Analog Scale (EQ-VAS), and the Patient Health Questionnaire 9 (PHQ-9). The cohort was divided up into 3 levels based on years of smoke exposure–no-reported smoke exposure (0 years), light exposure (1–19 years), and heavy exposure (20+ years), and independent-samples-Kruskal-Wallis testing was performed with post-hoc pairwise comparison and the Bonferroni correction. The results of this testing indicated significant increases in survey scores for patients with current biomass exposure and a heavy smoke exposure history (20+ years) compared to no reported smoke exposure in the SGRQ activity scores (adj. p = 0.018) and EQ-5D-3L usual activity scores (adj. p = 0.002), indicating worse activity related symptoms. There was a decrease in EQ-VAS scores for heavy (adj. p = 0.007) and light (adj. p = 0.017) exposure groups compared to no reported exposure, indicating lower perceptions of overall health. These results may suggest worse outcomes or baseline health for TB patients exposed to biomass smoke at the time of treatment and recovery, however further research is needed to characterize the effect of indoor air pollution on TB treatment outcomes.</div