Browsing by Author "Le Doare, Kirsty"

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    Etiology and Antimicrobial Resistance of Culture-Positive Infections in Ugandan Infants: A Cohort Study of 7000 Neonates and Infants
    (Oxford University Press, 2025-03) Davies, Hannah G;; Kyohere, Mary;; Tusubira, Valerie ;; Amone, Alexander;; Wamawobe, Amusa;; Komugisha, Cleophas;; Musoke, Philippa;; Hookham, Lauren;; Ravji, Pooja;; Etti, Melanie;; Nsimire Sendagala, Juliet;; Shelley, Dan R;; Farley, Caitlin;; Voysey, Merryn;; Spiller, Owen B;; Peacock, Joseph;; Sekikubo, Musa;; Heath, Paul T;; Le Doare, Kirsty
    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.BackgroundEpidemiological 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.MethodsBabies 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. Escherichia coli (14.8%), Acinetobacter spp. (10.3%), and Klebsiella spp. (7.6%), were notable contributors to Gram-negative sepsis, whereas Group B Streptococcus was the predominant Gram-positive pathogen identified (13.5%). Almost 60% of Gram-negative pathogens were ampicillin- and gentamicin-resistant.ResultsA 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. Escherichia coli (14.8%), Acinetobacter spp. (10.3%), and Klebsiella spp. (7.6%), were notable contributors to Gram-negative sepsis, whereas Group B Streptococcus 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.ConclusionsOur 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.
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    Infectious Causes of Stillbirths: A Descriptive Etiological Study in Uganda
    (Oxford University Press, 2025-03-10) Hookham, Lauren;; Tusubira, Valerie;; Wamawobe, Amusa ;; Shelley, Dan R;; Farley, Caitlin;; Portal, Edward A R;; Beach, Simon;; Davies, Hannah G;; Karampatsas, Konstantinos;; Kyohere, Mary;; Peacock, Joseph;; Musoke, Philippa;; Spiller, Owen B;; Heath, Paul T;; Sekikubo, Musa;; Le Doare, Kirsty
    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.BackgroundEvery 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.MethodsThe 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 Enterococcus spp. (n = 14), Escherichia coli (n = 13), viridans streptococci (n = 18), Klebsiella pneumoniae (n = 6), and group B Streptococcus (n = 5). Gram-negative organisms were frequently resistant to commonly used first-line antimicrobials.ResultsKawempe 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 Enterococcus spp. (n = 14), Escherichia coli (n = 13), viridans streptococci (n = 18), Klebsiella pneumoniae (n = 6), and group B Streptococcus (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.ConclusionsThe 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. MEDLINE - Academic
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    Maternal Vaccination in Uganda: Exploring Pregnant Women, Community Leaders and HealthcareWorkers’ Perceptions
    (MDPI, 2021) Nalubega, Phiona; Karafillakis, Emilie; Atuhaire, Lydia; Akite, Pamela; Zalwango, Flavia; Chantler, Tracey; Cochet, Madeleine; Seeley, Janet; Le Doare, Kirsty
    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.