Browsing by Author "Cummings, Matthew J."

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    A complex intervention to improve implementation of World Health Organization guidelines for diagnosis of severe illness in low-income settings: a quasi-experimental study from Uganda
    (Implementation Science, 2017) Cummings, Matthew J.; Goldberg, Elijah; Mwaka, Savio; Kabajaasi, Olive; Vittinghoff, Eric; Cattamanchi, Adithya; Katamba, Achilles; Kenya-Mugisha, Nathan; Jacob, Shevin T.; Davis, J. Lucian
    To improve management of severely ill hospitalized patients in low-income settings, the World Health Organization (WHO) established a triage tool called “Quick Check” to provide clinicians with a rapid, standardized approach to identify patients with severe illness based on recognition of abnormal vital signs. Despite the availability of these guidelines, recognition of severe illness remains challenged in low-income settings, largely as a result of infrequent vital sign monitoring. Methods: We conducted a staggered, pre-post quasi-experimental study at four inpatient health facilities in western Uganda to assess the impact of a multi-modal intervention for improving quality of care following formal training on WHO “Quick Check” guidelines for diagnosis of severe illness in low-income settings. Intervention components were developed using the COM-B (“capability,” “opportunity,” and “motivation” determine “behavior”) model and included clinical mentoring by an expert in severe illness care, collaborative improvement meetings with external support supervision, and continuous audits of clinical performance with structured feedback. Results: There were 5759 patients hospitalized from August 2014 to May 2015: 1633 were admitted before and 4126 during the intervention period. Designed to occur twice monthly, collaborative improvement meetings occurred every 2–4 weeks at each site. Clinical mentoring sessions, designed to occur monthly, occurred every 4–6 months at each site. Audit and feedback reports were implemented weekly as designed. During the intervention period, there were significant increases in the site-adjusted likelihood of initial assessment of temperature, heart rate, blood pressure, respiratory rate, mental status, and pulse oximetry. Patients admitted during the intervention period were significantly more likely to be diagnosed with sepsis (4.3 vs. 0.4%, risk ratio 10.1, 95% CI 3.0–31.0, p < 0.001) and severe respiratory distress (3.9 vs. 0.9%, risk ratio 4.5, 95% CI 1.8–10.9, p = 0.001). Conclusions: Theory-informed quality improvement programs can improve vital sign collection and diagnosis of severe illness in low-income settings. Further implementation, evaluation, and scale-up of such interventions are needed to enhance hospital-based triage and severe illness management in these settings.
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    Emergence, Epidemiology, and Transmission Dynamics of 2009 Pandemic A/H1N1 Influenza in Kampala, Uganda, 2009–2015
    (The American journal of tropical medicine and hygiene, 2018) Cummings, Matthew J.; Bakamutumaho, Barnabas; Yang, Wan; Wamala, Joseph F.; Kayiwa, John; Owor, Nicholas; Namagambo, Barbara; Byaruhanga, Timothy; Lutwama, Julius J.; Shaman, Jeffrey; O’Donnell, Max R.
    In sub-Saharan Africa, little is known about the epidemiology of pandemic-prone influenza viruses in urban settings. Using data from a prospective sentinel surveillance network, we characterized the emergence, epidemiology, and transmission dynamics of 2009 pandemic A/H1N1 influenza (H1N1pdm09) in Kampala, Uganda. After virus introduction via international air travel from England in June 2009, we estimated the basic reproductive number in Kampala to be 1.06–1.13, corresponding to attack rates of 12–22%. We subsequently identified 613 cases of influenza in Kampala from 2009 to 2015, of which 191 (31.2%) were infected with H1N1pdm09. Patients infected with H1N1pdm09 were more likely to be older adult (ages 35–64) males with illness onset during rainy season months. Urban settings in sub-Saharan Africa are vulnerable to importation and intense transmission of pandemic-prone influenza viruses. Enhanced surveillance and influenza pandemic preparedness in these settings is needed.
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    Multidimensional analysis of the host response reveals prognostic and pathogen-driven immune subtypes among adults with sepsis in Uganda
    (Critical Care, 2022) Cummings, Matthew J.; Bakamutumaho, Barnabas; Adam, Price; Owor, Nicholas; Kayiwa, John; Namulondo, Joyce; Byaruhanga, Timothy; Muwanga, Moses; Nsereko, Christopher; Stephen, Samerof; Rafal, Tokarz; Wai, Wong; Shivang, S. Shah; Michelle, H. Larsen; Lipkin, W. Ian; Lutwama, Julius J.; Max, R. O’Donnell
    Background The global burden of sepsis is concentrated in sub-Saharan Africa, where severe infections disproportionately affect young, HIV-infected adults and high-burden pathogens are unique. In this context, poor understanding of sepsis immunopathology represents a crucial barrier to development of locally-effective treatment strategies. We sought to determine inter-individual immunologic heterogeneity among adults hospitalized with sepsis in a sub-Saharan African setting, and characterize associations between immune subtypes, infecting pathogens, and clinical outcomes. Methods Among a prospective observational cohort of 288 adults hospitalized with suspected sepsis in Uganda, we applied machine learning methods to 14 soluble host immune mediators, reflective of key domains of sepsis immunopathology (innate and adaptive immune activation, endothelial dysfunction, fibrinolysis), to identify immune subtypes in randomly-split discovery (N = 201) and internal validation (N = 87) sub-cohorts. In parallel, we applied similar methods to whole-blood RNA-sequencing data from a consecutive subset of patients (N = 128) to identify transcriptional subtypes, which we characterized using biological pathway and immune cell-type deconvolution analyses. Results Unsupervised clustering consistently identified two immune subtypes defined by differential activation of pro-inflammatory innate and adaptive immune pathways, with transcriptional evidence of concomitant CD56(-)/CD16( +) NK-cell expansion, T-cell exhaustion, and oxidative-stress and hypoxia-induced metabolic and cell-cycle reprogramming in the hyperinflammatory subtype. Immune subtypes defined by greater pro-inflammatory immune activation, T-cell exhaustion, and metabolic reprogramming were consistently associated with a high-prevalence of severe and often disseminated HIV-associated tuberculosis, as well as more extensive organ dysfunction, worse functional outcomes, and higher 30-day mortality. Conclusions Our results highlight unique host- and pathogen-driven features of sepsis immunopathology in sub-Saharan Africa, including the importance of severe HIV-associated tuberculosis, and reinforce the need to develop more biologically-informed treatment strategies in the region, particularly those incorporating immunomodulation.
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    Severe COVID-19 in Uganda across Two Epidemic Phases: A Prospective Cohort Study
    (The American journal of tropical medicine and hygiene, 2021) Bakamutumaho, Barnabas; Cummings, Matthew J.; Owor, Nicholas; Kayiwa, John; Namulondo, Joyce; Byaruhanga, Timothy; Muwanga, Moses; Nsereko, Christopher; Mutonyi, Roselyn; Achan, Josephine; wanyenze, Lucy; Ndazarwe, Alice; Nakanjako, Ruth; Natuhwera, Richard; Nsangi, Annet; Bosa, Henry Kyobe; Ocom, Felix; Kikaire, Bernard; Lutwama, Julius J.
    Among a prospective cohort of children and adults admitted to a national COVID-19 treatment unit in Uganda from March to December 2020, we characterized the epidemiology of and risk factors for severe illness. Across two epidemic phases differentiated by varying levels of community transmission, the proportion of patients admitted with WHO-defined severe COVID-19 ranged from 5% (7/146; 95% CI: 2–10) to 33% (41/124; 95% CI: 25–42); 21% (26/124; 95% CI: 14–29%) of patients admitted during the peak phase received oxygen therapy. Severe COVID-19 was associated with older age, male sex, and longer duration of illness before admission. Coinfection with HIV was not associated with illness severity; malaria or tuberculosis coinfection was rare. No patients died during admission. Despite low mortality, hospital incidence of severe COVID-19 during the first epidemic peak in Uganda was substantial. Improvements in vaccine deployment and acute care capacity, including oxygen delivery, are urgently needed to prevent and manage severe COVID-19 in sub-Saharan Africa.