Chronic pulmonary aspergillosis commonly complicates treated pulmonary tuberculosis with residual cavitation.

Chronic pulmonary aspergillosis (CPA) complicates treated pulmonary tuberculosis (TB), with high 5-year mortality. We measured CPA prevalence in this group.398 Ugandans with treated pulmonary TB underwent clinical assessment, chest radiography and Aspergillus-specific IgG measurement. 285 were resurveyed 2 years later, including computed tomography of the thorax in 73 with suspected CPA. CPA was diagnosed in patients without active TB who had raised Aspergillus-specific IgG, radiological features of CPA and chronic cough or haemoptysis.Author-defined CPA was present in 14 (4.9%, 95% CI 2.8-7.9%) resurvey patients. CPA was significantly more common in those with chest radiography cavitation (26% versus 0.8%; p<0.001), but possibly less frequent in HIV co-infected patients (3% versus 6.7%; p=0.177) The annual rate of new CPA development between surveys was 6.5% in those with chest radiography cavitation and 0.2% in those without (p<0.001). Absence of cavitation and pleural thickening on chest radiography had 100% negative predictive value for CPA. The combination of raised Aspergillus-specific IgG, chronic cough or haemoptysis and chest radiography cavitation had 85.7% sensitivity and 99.6% specificity for CPA diagnosis.CPA commonly complicates treated pulmonary TB with residual chest radiography cavitation. Chest radiography alone can exclude CPA. Addition of serology can diagnose CPA with reasonable accuracy.

Characterization of Antibiotic Resistance in Select Tertiary Hospitals in Uganda: An Evaluation of 2020 to 2023 Routine Surveillance Data.

Antimicrobial resistance (AMR) is a public health concern in Uganda. We sought to conduct an extended profiling of AMR burden at selected Ugandan tertiary hospitals. We analyzed routine surveillance data collected between October 2020 and March 2023 from 10 tertiary hospitals. The analysis was stratified according to the hospital unit, age, gender, specimen type, and time. Up to 2754 isolates were recovered, primarily from pus: 1443 (52.4%); urine: 1035 (37.6%); and blood: 245 (8.9%). Most pathogens were Staphylococcus aureus, 1020 (37%), Escherichia coli, 808 (29.3%), and Klebsiella spp., 200 (7.3%). Only 28% of Escherichia coli and 42% of the other Enterobacterales were susceptible to ceftriaxone, while only 44% of Staphylococcus aureus were susceptible to methicillin (56% were MRSA). Enterococcus spp. susceptibility to vancomycin was 72%. The 5-24-year-old had 8% lower ampicillin susceptibility than the >65-year-old, while the 25-44-year-old had 8% lower ciprofloxacin susceptibility than the >65-year-old. The 0-4-year-old had 8% higher ciprofloxacin susceptibility. Only erythromycin susceptibility varied by sex, being higher in males. Escherichia coli ciprofloxacin susceptibility in blood (57%) was higher than in urine (39%) or pus (28%), as was ceftriaxone susceptibility in blood (44%) versus urine (34%) or pus (14%). Klebsiella spp. susceptibility to ciprofloxacin and meropenem decreased by 55% and 47%, respectively, during the evaluation period. During the same period, Escherichia coli ciprofloxacin susceptibility decreased by 40%, while Staphylococcus aureus gentamicin susceptibility decreased by 37%. Resistance was high across the Access and Watch antibiotic categories, varying with time, age, sex, specimen type, and hospital unit. Effective antimicrobial stewardship targeted at the critical AMR drivers is urgently needed.

Spike protein is a key target for stronger and more persistent T-cell responses-a study of mild and asymptomatic SARS-CoV-2 infection.

OBJECTIVES: Understanding the immune response in very mild and asymptomatic COVID-19 is crucial for developing effective vaccines and immunotherapies, yet remains poorly characterized. This longitudinal study examined the evolution of interferon (IFN)-γ responses to SARS-CoV-2 peptides in 109 asymptomatic or mildly symptomatic Ugandan COVID-19 patients across 365 days and explored their association with antibody generation. METHODS: T-cell responses to spike-containing clusters of differentiation (CD4)-S and CD8 nCoV-A (CD8-A) megapools, and the non-spike CD4-R and CD8 nCoV-B (CD8-B) megapools, were assessed and correlated with demographic and temporal variables. RESULTS: SARS-CoV-2-specific IFN-γ responses were consistently detected in all peptide pools and time points, with the spike-targeted response exhibiting higher potency and durability than the non-spike responses. Throughout the entire 365-day infection timeline, a robust positive correlation was observed between CD4 T-cell responses to the spike-derived peptides and anti-spike immunoglobulin G antibody levels, underscoring their interdependent dynamics in the immune response against SARS-CoV-2; in contrast, CD8 T-cell responses exhibited no such correlation, highlighting their distinctive, autonomous role in defense. No meaningful variations in complete blood count parameters were observed between individuals with COVID-19 infection and those without, indicating clinical insignificance. CONCLUSIONS: This study highlights the dominant role of spike-directed T-cell responses in mild and asymptomatic disease and provides crucial longitudinal data from Sub-Saharan African settings. The findings provide valuable insights into the dynamics of T-cell responses and their potential significance in developing effective strategies for combating COVID-19.

Rapid, early, and potent Spike-directed IgG, IgM, and IgA distinguish asymptomatic from mildly symptomatic COVID-19 in Uganda, with IgG persisting for 28 months.

Introduction: Understanding how spike (S)-, nucleoprotein (N)-, and RBD-directed antibody responses evolved in mild and asymptomatic COVID-19 in Africa and their interactions with SARS-CoV-2 might inform development of targeted treatments and vaccines. Methods: Here, we used a validated indirect in-house ELISA to characterise development and persistence of S- and N-directed IgG, IgM, and IgA antibody responses for 2430 SARS-CoV-2 rt-PCR-diagnosed Ugandan specimens from 320 mild and asymptomatic COVID-19 cases, 50 uninfected contacts, and 54 uninfected non-contacts collected weekly for one month, then monthly for 28 months. Results: During acute infection, asymptomatic patients mounted a faster and more robust spike-directed IgG, IgM, and IgA response than those with mild symptoms (Wilcoxon rank test, p-values 0.046, 0.053, and 0.057); this was more pronounced in males than females. Spike IgG antibodies peaked between 25 and 37 days (86.46; IQR 29.47-242.56 BAU/ml), were significantly higher and more durable than N- and RBD IgG antibodies and lasted for 28 months. Anti-spike seroconversion rates consistently exceeded RBD and nucleoprotein rates. Spike- and RBD-directed IgG antibodies were positively correlated until 14 months (Spearman's rank correlation test, p-values 0.0001 to 0.05), although RBD diminished faster. Significant anti-spike immunity persisted without RBD. 64% and 59% of PCR-negative, non-infected non-contacts and suspects, exhibited baseline SARS-CoV-2 N-IgM serological cross-reactivity, suggesting undetected exposure or abortive infection. N-IgG levels waned after 787 days, while N-IgM levels remained undetectable throughout. Discussion: Lower N-IgG seroconversion rates and the absence of N-IgM indicate that these markers substantially underestimate the prior exposure rates. Our findings provide insights into the development of S-directed antibody responses in mild and asymptomatic infections, with varying degrees of symptoms eliciting distinct immune responses, suggesting distinct pathogenic pathways. These longer-lasting data inform vaccine design, boosting strategies, and surveillance efforts in this and comparable settings.

Efficacy and acceptability of an acute illness management course delivered to staff and students in Uganda by staff from the UK.

BACKGROUND: Recent reviews report that healthcare professionals have limited training in managing acutely ill patients and that significant gains could be made in low-income countries by focussing on care of the critically ill. We aimed to determine if a UK-developed acute illness management course (AIM) was acceptable to staff and students in a low-income country and if it improved their knowledge. METHODS: A total of 188 students and staff attended one of 8 one-day courses teaching a systematic approach to the recognition, assessment and management of acutely ill patients. RESULTS: A pre and post course test of knowledge was completed by 146/188 participants (77.7%) with a significant (p<0.001) increase in knowledge post course. Median increases in percentage scores by professional group ranged from 16-24%. A questionnaire about their experiences of the course and their intentions to use the AIM approach was completed by 81/188 participants (43.1%). The course was acceptable and participants indicated a high level of intention to use the approach. CONCLUSIONS: A UK-developed acute illness management course was acceptable in a low-income country and delivered significant increases in knowledge and a high intention to change practice. Future research must focus on understanding the implementation of education into clinical practice.