TY  - JOUR
AB  - BACKGROUND: Half the global tuberculosis health burden is due to post-tuberculosis lung disease. Host-directed therapies have been proposed to reduce this burden. N-acetylcysteine (NAC) provides the conditionally essential amino acid cysteine required for synthesis of glutathione, an antioxidant thiol. We recently reported clinical outcomes of a trial of adjunctive NAC in patients with pulmonary tuberculosis, finding that NAC improved the secondary endpoint of recovery of lung function. Here we report the effects of NAC on biomarkers of oxidation, inflammation, and infection in that trial. METHODS: 140 adults with moderate or far-advanced pulmonary tuberculosis were randomly assigned to standard tuberculosis treatment with or without NAC 1200mg twice daily for months 1-4. Sputum and blood samples were obtained at specified intervals to measure total glutathione, MTB-induced cytokines, haemoglobin, whole blood mycobactericidal activity (WBA), and sputum MTB burden. RESULTS: NAC treatment rapidly increased total glutathione (P<.0001), but levels did not reach those of healthy volunteers (P<.001). NAC reduced MTB-induced TNF-α (P =.011) without affecting IL-10, and accelerated the recovery of hemoglobin in participants with low values on entry. NAC did not affect killing in ex vivo whole blood culture but did slow the clearance of MTB from sputum (P=0.003). CONCLUSION: Adjunctive NAC showed antioxidant and anti-inflammatory effects consistent with the amelioration of immunopathology seen in preclinical models. Two biomarkers of antimicrobial activity showed discordant results; neither demonstrated the enhanced antimicrobial effects seen preclinically. The reduction of oxidative stress and inflammation by NAC may explain its effects on the recovery of lung function post-TB.
AU  - Mapamba, D.A.*
AU  - Sabi, I.*
AU  - Lalashowi, J.*
AU  - Sauli, E.*
AU  - Buza, J.*
AU  - Olomi, W.*
AU  - Mtafya, B.*
AU  - Kibona, M.*
AU  - Bakhuli, A.*
AU  - Rachow, A.
AU  - Velen, K.*
AU  - Hoelscher, M.
AU  - Ntinginya, N.E.*
AU  - Charalambous, S.*
AU  - Churchyard, G.*
AU  - Wallis, R.S.*
C1  - 72951
C2  - 56882
CY  - 32 Jamestown Rd, London Nw1 7by, England
TI  - N-acetylcysteine modulates markers of oxidation, inflammation and infection in tuberculosis.
JO  - J. Infect.
VL  - 90
IS  - 2
PB  - W B Saunders Co Ltd
PY  - 2025
SN  - 0163-4453
ER  - 

TY  - JOUR
AB  - BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), affects around 6-7 million people in Latin America and hundreds of thousands in the United States and Europe. A main complication of chronic Chagas disease is cardiomyopathy, possibly manifesting as arrhythmias, heart failure, or sudden cardiac death. Understanding the link between T. cruzi infection and cardiomyopathy is essential for early diagnosis and adequate treatment. METHODS: We sequenced small RNAs in serum samples from 228 Chagas patients recruited in Chile, Bolivia and Italy. After bioinformatic processing of sequencing data to quantify serum miRNA expression, robust logistic regression was applied to identify miRNAs differentially expressed in Chagas patients with abnormalities in electrocardiography (ECG), bundle-branch block on ECG, and high Kuschnir scores. We also investigated the association between genotype-based miRNA expression and the risk of abnormal ECG findings. FINDINGS: As reported, the risk of abnormal ECG findings was higher in male patients and increased with age. Three miRNAs showed lower serum expression levels in patients with abnormal ECG: miRNA-101-3p, miRNA-576-3p and miRNA-629-5p (p < 0.0002), especially in patients with high Kuschnir scores. The expression of miRNA-629-5p was negatively correlated with the CCL5 expression (p = 3.7×10-8), a chemokine frequently reported in Chagas disease, gene enrichment analyses indicated involvement of cytokine signalling in Chagas cardiomyopathy. INTERPRETATION: The findings demonstrate the potential of circulating miRNAs as diagnostic biomarkers for Chagas cardiomyopathy. The associations found with disease severity and immune response may help to improve our knowledge of complications' development in Chagas disease.
AU  - Mueller, M.*
AU  - Blandino, A.*
AU  - Scherer, D.*
AU  - Zulantay, I.*
AU  - Apt, W.*
AU  - Varela, N.M.*
AU  - Llancaqueo, M.*
AU  - Garcia, L.*
AU  - Ortiz, L.*
AU  - Nicastri, E.*
AU  - Giancola, M.L.*
AU  - Angheben, A.*
AU  - Gabrielli, S.*
AU  - Rounge, T.B.*
AU  - Langseth, H.*
AU  - Waldenberger, M.
AU  - Salinas-Alvarez, P.*
AU  - Bermejo, J.L.*
C1  - 75565
C2  - 57941
CY  - 32 Jamestown Rd, London Nw1 7by, England
TI  - Small-RNA sequencing identifies serum microRNAs associated with abnormal electrocardiography findings in patients with Chagas disease.
JO  - J. Infect.
VL  - 91
IS  - 4
PB  - W B Saunders Co Ltd
PY  - 2025
SN  - 0163-4453
ER  - 

TY  - JOUR
AB  - OBJECTIVES: The risk of Post-COVID-19 condition (PCC) under hybrid immunity remains unclear. METHODS: Using data from the German National Cohort (NAKO Gesundheitsstudie), we investigated risk factors for self-reported post-infection symptoms (any PCC is defined as having at least one symptom, and high symptom burden PCC as having nine or more symptoms). RESULTS: Sixty percent of 109,707 participants reported at least one previous SARS-CoV-2 infection; 35% reported having had any symptoms 4-12 months after infection; among them 23% reported nine or more symptoms. Individuals, who did not develop PCC after their first infection, had a strongly reduced risk for PCC after their second infection (50%) and a temporary risk reduction, which waned over nine months after the preceding infection. The risk of developing PCC strongly depended on the virus variant. Within variants, there was no effect of the number of preceding vaccinations, apart from a strong protection by the fourth vaccination compared to three vaccinations for the Omicron variant (odds ratio=0.52; 95% confidence interval 0.45-0.61). CONCLUSIONS: Previous infections without PCC and a fourth vaccination were associated with a lower risk of PCC after a new infection, indicating diminished risk under hybrid immunity. The two components of risk reduction after a preceding infection suggest different immunological mechanisms.
AU  - Mikolajczyk, R.*
AU  - Diexer, S.*
AU  - Klee, B.*
AU  - Pfrommer, L.*
AU  - Purschke, O.*
AU  - Fricke, J.*
AU  - Ahnert, P.*
AU  - Gabrysch, S.*
AU  - Gottschick, C.*
AU  - Bohn, B.*
AU  - Brenner, H.*
AU  - Buck, C.*
AU  - Castell, S.*
AU  - Gastell, S.*
AU  - Greiser, K.H.*
AU  - Harth, V.*
AU  - Heise, J.K.*
AU  - Holleczek, B.*
AU  - Kaaks, R.*
AU  - Keil, T.*
AU  - Krist, L.*
AU  - Leitzmann, M.*
AU  - Lieb, W.*
AU  - Meinke-Franze, C.*
AU  - Michels, K.B.*
AU  - Velásquez, I.M.*
AU  - Obi, N.*
AU  - Panreck, L.*
AU  - Peters, A.
AU  - Pischon, T.*
AU  - Schikowski, T.*
AU  - Schmidt, B.*
AU  - Standl, M.
AU  - Stang, A.*
AU  - Völzke, H.*
AU  - Weber, A.*
AU  - Zeeb, H.*
AU  - Karch, A.*
C1  - 70881
C2  - 55788
CY  - 32 Jamestown Rd, London Nw1 7by, England
SP  - 7
TI  - Likelihood of Post-COVID Condition in people with hybrid immunity; data from the German National Cohort (NAKO).
JO  - J. Infect.
VL  - 89
IS  - 2
PB  - W B Saunders Co Ltd
PY  - 2024
SN  - 0163-4453
ER  - 

TY  - JOUR
AB  - Community Acquired Pneumonia (CAP) is a frequent and potentially fatal infectious disease which, in the majority of cases, needs an antibiotic intervention.Objectives: Aim was to evaluate antibiotic treatment patterns regarding all types of mono- and combination-therapy throughout the local clinical centres (LCCs) represented in the German competence network CAPNETZ (= Community Acquired Pneumonia Network) and to identify clinical indicators for regional differences.Methods: We analysed outpatients and inpatients recruited between March 2003 and April 2005. Patient and treatment details were registered online using standardised data entry forms. A logistic regression model was issued for the 4 most frequently applied antibiotics, adjusting for potentially relevant confounders.Results: The study sample consisted of 3221 patients at the age of 18 to 102 years. Overall, aminopenicillins plus betalactamase inhibitor (20.4%), fluoroquinolone (17.0%), macrolides combined with cephalosporins third generation (10.6%) and cephalosporins third generation (8.9%) were most frequently prescribed. After control for potential confounders, significant treatment differences remained between study sites.
AU  - Kohlhammer, Y.
AU  - Raspe, H.*
AU  - Marre, R.*
AU  - Suttorp, N.*
AU  - Welte, T.*
AU  - Schäfer, T.*
C1  - 3919
C2  - 24497
SP  - 446-453
TI  - Antibiotic treatment of community acquired pneumonia varies widely across Germany.
JO  - J. Infect.
VL  - 54
IS  - 5
PB  - Elsevier
PY  - 2007
SN  - 0163-4453
ER  - 

TY  - JOUR
AB  - Despite strong recommendations, immunization rates for influenza and pneumococci are low. We aimed to analyse the vaccination status and its determinants in patients with chronic lung diseases. METHODS: Information about actual influenza (IV) and pneumococcal (PV) vaccination status was obtained by a standardised questionnaire from 2491 patients presenting to a specialised centre of respiratory medicine in Rotenburg/Wuemme (Germany). Bivariate and multivariate analyses were used to identify potential determinants of IV and PV. RESULTS: Of 2131 patients with asthma and/or COPD, included into detailed analyses (52.0% male, mean age 56.6 years), 46.5% had received an IV and 14.6% a PV. Main reason for not being vaccinated was the lack of information, reaching 87.6% for PV (53.5% for IV); 37.0% saw no reason for an IV (PV 21.3%). Vaccination rates differed depending on the patients' age and education level. CONCLUSION: The results indicate a marked information deficit on immunization which is explicitly higher for PV. Target-group-specific strategies should increase the knowledge on vaccinations in order to avoid the development or aggravation of acute and chronic lung diseases.
AU  - Schoefer, Y.
AU  - Schaberg, T.
AU  - Raspe, H.*
AU  - Schaefer, T.*
C1  - 920
C2  - 27291
SP  - 347-352
TI  - Determinants of influenza and pneumococcal vaccination in patients with chronic lung diseases.
JO  - J. Infect.
VL  - 55
IS  - 4
PB  - British Infection Soc.
PY  - 2007
SN  - 0163-4453
ER  -