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Background: We investigated pregnant women, community leaders, healthcare workers (HCWs) and programme managers’ perceptions of maternal vaccination in Kampala, Uganda. Methods: We conducted focus group discussions, key informant interviews and in-depth discussions with HCWs (3), community leaders (3), pregnant women (8) and programme managers (10) between November 2019 and October 2020. Data were analysed thematically. Results: Pregnant women, community leaders and some HCWs had limited maternal immunisation knowledge. There was confusion over what constitutes a vaccine. Pregnant women may not receive vaccines because of mistrust of government; use of expired vaccines; reliance on traditional medicine; religious beliefs; fear of side effects; HCWs attitudes; and logistical issues. The key facilitators of maternal vaccination were a desire to prevent diseases, positive influences from HCWs and information about vaccine side effects. Community leaders and some pregnant women highlighted that pregnant women do not make decisions about maternal vaccination independently and are influenced by different individuals, including other pregnant women, older people, partners, relatives (parents), community leaders, HCWs and the government. Conclusions: Our results indicate that public health messaging should target all community members, including partners and parents of pregnant women as well as HCWs, to improve knowledge of and confidence in maternal vaccines.

Biomarker measures of infarct size and myocardial salvage index (MSI) are important surrogate measures of clinical outcomes after a myocardial infarction. However, there is variability in infarct size unaccounted for by conventional adjustment factors. This post hoc analysis of Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events (EMBRACE) ST-Segment Elevation Myocardial Infarction (STEMI) trial evaluates the association between left ventricular (LV) mass and infarct size as assessed by areas under the curve for creatine kinase-MB (CK-MB) and troponin I release over the first 72 hours (CK-MB area under the curve [AUC] and troponin I [TnI] AUC) and the MSI. Patients with first anterior STEMI, occluded left anterior descending artery, and available LV mass measurement in EMBRACE STEMI trial were included (n = 100) (ClinicalTrials.govNCT01572909). MSI, end-diastolic LV mass on day 4 cardiac magnetic resonance, and CK-MB and troponin I concentrations were evaluated by a core laboratory. After saturated multivariate analysis, dominance analysis was performed to estimate the contribution of each independent variable to the predicted variance of each outcome. In multivariate models that included age, gender, body surface area, lesion location, smoking, and ischemia time, LV mass remained independently associated with biomarker measures of infarct size (CK-MB AUC p = 0.02, TnI AUC p = 0.03) and MSI (p = 0.003). Dominance analysis demonstrated that LV mass accounted for 58%, 47%, and 60% of the predicted variances for CK-MB AUC, TnI AUC, and MSI, respectively. In conclusion, LV mass accounts for approximately half of the predicted variance in biomarker measures of infarct size. It should be considered as an adjustment variable in studies evaluating infarct size.

Crystallographic analysis of human Hfe has documented an overall structure similar to classical (class la) MHC molecules with a peptide binding groove deprived of ligand. Thus, to address the question of whether αβ T cells could recognize MHC molecules independently of bound ligands, we studied human and mouse Hfe interactions with T lymphocytes. We provide formal evidence of direct cytolytic recognition of human Hfe by mouse αβ T cell receptors (TCR) in HLA-A*0201 transgenic mice and that this interaction results in ZAP-70 phosphorylation. Furthermore, direct recognition of mouse Hfe molecules by cytotoxic T lymphocytes (CTLs) was demonstrated in DBA/2 Hfe knockout mice. These CTLs express predominantly two T cell antigen receptor α variable gene segments (AV6.1 and AV6.6). Interestingly, in wild-type mice we identified a subset of CD8+T cells positively selected by Hfe that expresses the AV6.1/AV6.6 gene segments. T cell antigen receptor recognition of MHC molecules independently of bound ligand has potential general implications in alloreactivity and identifies in the Hfe case a cognitive link supporting the concept that the immune system could be involved in the control of iron metabolism.

•Point estimates of the half-life of transplacental anti-GBS IgG were 23–28 days.•Strong correlation between IgG concentrations at birth and one month of age.•Antibody kinetics may help in defining a correlate of protection against GBS LOD. Capsular polysaccharide (CPS) serotype-specific Immunoglobulin G (IgG) in cord blood has been proposed as a correlate of protection against invasive Group B Streptococcus (iGBS) disease. Although protective levels are required in infants throughout the window of vulnerability up to 3 months of age, little is known regarding the kinetics of GBS-specific IgG over this period. We enrolled 33 healthy infants born to mothers colonized with GBS. We collected cord blood and infant blood samples either at one (21–35 days), two (49–63 days), or three months of age (77–91 days). We measured GBS serotype-specific CPS IgG concentrations and calculated the decay rate using a mixed-effects model. We further explored whether the antibody kinetics were affected by common maternal and infant factors and estimated the correlation between IgG concentration at birth and one, two, and three months of age. The half-life estimate of IgG concentration for homologous and non-homologous GBS serotypes in paired samples with detectable IgG levels at both time points was 27.4 (95 % CI: 23.5–32.9) days. The decay rate did not vary by maternal age (p = 0.7), ethnicity (p = 0.1), gravida (p = 0.1), gestation (p = 0.7), and infant sex (p = 0.1). Predicted IgG titres above the assay lower limit of quantification on day 30 strongly correlated with titres at birth (Spearman correlation coefficient 0.71 [95 % CI: 0.60–0.80]). Our results provide a basis for future investigations into the use of antibody kinetics in defining a serocorrelate of protection against late-onset iGBS disease.

Epidemiological evidence about the etiology and antimicrobial resistance of neonatal infections remains limited in low-resource settings. We aimed to describe the etiology of neonatal infections in a prospective observational cohort study conducted at two hospital sites in Kampala, Uganda. Babies admitted to either unit with risk factors or signs of sepsis, pneumonia, or meningitis had a blood culture, nasopharyngeal swab, and lumbar puncture (if indicated) collected. Basic demographics were collected, and babies were followed up until discharge or death to determine admission outcome. Blood cultures were processed using the BACTEC system and identification confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Cerebrospinal fluid was processed using standard microbiological testing and swabs were processed using the multiplex real-time polymerase chain reaction assay. Antimicrobial susceptibilities of bacterial isolates to World Health Organization-recommended first-line antibiotics (ampicillin or benzylpenicillin and gentamicin) were assessed using e-tests. A total of 7323 infants with signs or risk factors for sepsis had blood cultures, 2563 had nasopharyngeal swabs, and 23 had lumbar punctures collected. Eleven percent of blood cultures and 8.6% of swabs were positive. Inpatient mortality was 12.1%, with 27.7% case fatality observed among infants with Gram-negative bloodstream infections. (14.8%), spp. (10.3%), and spp. (7.6%), were notable contributors to Gram-negative sepsis, whereas Group B was the predominant Gram-positive pathogen identified (13.5%). Almost 60% of Gram-negative pathogens were ampicillin- and gentamicin-resistant. Our study demonstrates high levels of antimicrobial resistance and inpatient mortality from neonatal sepsis in the first months of life in Uganda. This underscores the pressing need for revised, context-specific antimicrobial treatment guidelines that account for the evolving landscape of antimicrobial resistance in neonatal sepsis.

Maternal Group B (GBS) rectovaginal colonization is an important risk factor for invasive disease in neonates, yet availability of culture-based methods for detection is limited in low-resource settings. We evaluated the diagnostic performance of the HiberGene (HG) GBS loop-mediated isothermal amplification (LAMP) assay for the rapid detection of GBS in rectal/vaginal swabs collected from women in Uganda. This work forms a part of the PROGRESS GBS study. In phase 1, 1294 rectal and vaginal swabs were collected from pregnant women and inoculated in enrichment (Lim) broth, which was then tested using the HG GBS LAMP assay ( gene target) and culture on chromogenic agar. In phase 2, 166 swabs from nonpregnant women were tested directly (without the enrichment step). For samples with discordant results, an additional method of testing against multiplex real-time polymerase chain reaction assay was used. Overall, the HG GBS LAMP assay detected more GBS-positive samples (31.3%; 452/1445) than culture-based methods (13.3%; 192/1445). Multiplex polymerase chain reaction-tested results were concordant with LAMP results in 96.3% of cases. The sensitivity and specificity of the LAMP assay, after adjusting for the tiebreaker results of discordant samples, were 94.4% (95% confidence interval, 86.2-99.4) and 99.0% (95% confidence interval, 94.3-100), respectively. The results of this study demonstrate high sensitivity and specificity of the HG GBS LAMP assay for the detection of GBS rectovaginal colonization in our setting. Given its rapid turnaround time, the HG GBS LAMP assay could appropriately be used to screen women for GBS rectovaginal colonization during labor to enable provision of intrapartum antibiotic prophylaxis.

We investigated awareness of neonatal infections among a population of pregnant women and other community members in Kampala, Uganda. We explored perceived causes of neonatal infections and perceptions of appropriate treatments. We conducted focus group discussions (FGDs) and in-depth interviews (IDIs) with 97 participants: 25 community leaders who took part in 3 FGDs, 12 pregnant women who took part in IDIs, and 60 pregnant women who took part in 8 FGDs, between November 2019 and October 2020. Data were analyzed thematically. This work formed part of the PROGRESS study, an observational cohort study undertaken in Kampala, Uganda, between November 2018 and April 2021. Beliefs about causes, signs, symptoms, and treatment of infants with suspected infections impacted health-seeking behavior. Some illnesses were perceived to be caused by environmental factors while others were believed to have social or behavioral causes, such as the promiscuity of the male partner causing infections or the mother being bewitched. Local herbs and traditional remedies were the most preferred method of treatment and were commonly relied on to address various health issues rather than conventional medicines. Notably, no participant mentioned vaccines as a way of preventing infections. Pregnant women and community members' understanding of the causes and treatment of neonatal illnesses were diverse, including environmental, social-behavioral, and supernatural causes, while both conventional and traditional remedies were perceived as appropriate treatments and sought accordingly. Understanding community perceptions and practices around neonatal infections is key to improving neonatal health interventions and outcomes.

Low- and middle-income countries lack data on culture-confirmed sepsis in HIV-exposed infants, despite the reported heightened risk of infectious morbidity. This study describes culture-confirmed sepsis and antibiotic resistance patterns among HIV-exposed children in a large etiological cohort study in Kampala, Uganda. This was a prospective birth cohort study based at 2 Ugandan sites, as part of the Progressing Group B Streptococcal Vaccines (PROGRESS) study. Any infant with risk factors, signs, or symptoms of infection presenting before 3 months of age had a blood culture and nasopharyngeal swab taken to determine the etiology of neonatal and young infant sepsis. Among 4492 blood cultures, 460 were obtained from HIV-exposed infants. Nine infants (1.9%) had positive blood cultures. The most frequently isolated organisms were , group B , and , and these organisms demonstrated resistance to the common antibiotics (aminoglycosides, penicillins, and cephalosporins) used for management of suspected sepsis. A higher proportion of the exposed babies died vs HIV-unexposed (15.8 vs 11.2; = .005). Nasopharyngeal swabs were collected from 114 infants, with 7.9% positive for at least one virus or bacterium. Future work is needed to investigate why mortality among HIV-exposed infants persists despite maternal antiretroviral treatment. Antimicrobial resistance is an increasing concern in this setting.

Every year an estimated 2-3 million babies are stillborn, with a high burden in Africa. Infection is an important driver of stillbirth. There is a lack of data on the bacterial causes of stillbirth in Uganda, contributing to a lack of interventions such as effective prophylaxis and development of maternal vaccine options against the most implicated pathogens. The PROGRESS study was an observational cohort study undertaken in Kampala, Uganda, between November 2018 and April 2021. If a woman delivered a stillborn baby, consent was sought for the collection of a heart-blood aspirate. One to three mL of blood was collected and sent for culture using the BD Bactec blood culture system. Organism identification was performed using biochemical testing and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Susceptibilities to appropriate panels of antimicrobials were determined by agar dilution. Kawempe Hospital registered 34 517 births in the study period, of which 1717 (5.0%) were stillbirths. A total of 581 (33.8%) were recruited into the study, and heart blood aspirates were performed on 569 (97.9%). Blood samples were sufficient for analysis of 476, with a total of 108 positive cultures (22.7% of sampled stillbirths). Fifty-nine of 108 blood cultures contained organisms that were considered potential pathogens, giving a pathogen positivity rate of 12.4%. Common pathogens included spp. (n = 14), (n = 13), viridans streptococci (n = 18), (n = 6), and group B (n = 5). Gram-negative organisms were frequently resistant to commonly used first-line antimicrobials. The high proportion of stillbirths caused by likely pathogenic bacteria in Uganda highlights the potential for prevention with prophylaxis and stresses the need for further investment in this area.

Hepatitis B virus (HBV) infection is a significant cause of morbidity and mortality globally. The World Health Organization estimates that just 10.5% of individuals living with HBV globally are aware of their status. Antenatal care provides an opportunity to screen pregnant women for HBV and to treat those who are eligible to reduce the risk of vertical transmission. We conducted an observational study to determine the proportion of pregnant women with active HBV infection delivering at a government-funded hospital in Kampala, Uganda, to estimate the number of missed opportunities to prevent vertical transmission. Eligible participants were enrolled via the PROGRESS study, an observational cohort study undertaken in Kampala, Uganda, between November 2018 and April 2021. Results presented here describe data from April 2019 to November 2020. Five milliliters of venous blood was drawn shortly after delivery. Serum aliquots were analyzed for hepatitis B surface antigen (HBsAg). HBsAg-positive participants were informed of their result by telephone and referred to the gastroenterology service for specialist management. In total, 6062 women were enrolled between April 2019 and November 2020. Results were available for 6012 (99.6%) participants, among whom 131 (2.2%) were HBsAg positive. Only 10 of 131 (7.6%) HBsAg-positive participants were successfully referred to the gastroenterology service at Mulago Hospital for treatment of their infection. Our study identified a number of missed opportunities to identify active HBV infection among our pregnant cohort. Additional resources are urgently required to increase the coverage of antenatal HBV screening while also improving treatment pathways for pregnant women with HBV infection in this region.