Browsing by Author "Bakamutumaho, Barnabas"

Now showing 1 - 8 of 8
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    COVID-19 immune signatures in Uganda persist in HIV co-infection and diverge by pandemic phase
    (Nature Publishing Group, 2024-02) Cummings, Matthew J; Bakamutumaho, Barnabas; Lutwama, Julius J; Owor, Nicholas; Che, Xiaoyu; Astorkia, Maider; Postler, Thomas S; Kayiwa, John; Kiconco, Jocelyn; Muwanga, Moses; Nsereko, Christopher; wamutwe, Emmanuel; Nayiga, Irene; Kyebambe, Stephen; Haumba, Mercy; Bosa, Henry Kyobe; Ocom, Felix; Watyaba, Benjamin; TKikaire, Bernard; Tomoiaga, Alin S; Kisaka, Stevens; Kiwanuka, Noah; Lipkin, W Ian; O'Donnell, Max R
    Little is known about the pathobiology of SARS-CoV-2 infection in sub-Saharan Africa, where severe COVID-19 fatality rates are among the highest in the world and the immunological landscape is unique. In a prospective cohort study of 306 adults encompassing the entire clinical spectrum of SARS-CoV-2 infection in Uganda, we profile the peripheral blood proteome and transcriptome to characterize the immunopathology of COVID-19 across multiple phases of the pandemic. Beyond the prognostic importance of myeloid cell-driven immune activation and lymphopenia, we show that multifaceted impairment of host protein synthesis and redox imbalance define core biological signatures of severe COVID-19, with central roles for IL-7, IL-15, and lymphotoxin-α in COVID-19 respiratory failure. While prognostic signatures are generally consistent in SARS-CoV-2/HIV-coinfection, type I interferon responses uniquely scale with COVID-19 severity in persons living with HIV. Throughout the pandemic, COVID-19 severity peaked during phases dominated by A.23/A.23.1 and Delta B.1.617.2/AY variants. Independent of clinical severity, Delta phase COVID-19 is distinguished by exaggerated pro-inflammatory myeloid cell and inflammasome activation, NK and CD8+ T cell depletion, and impaired host protein synthesis. Combining these analyses with a contemporary Ugandan cohort of adults hospitalized with influenza and other severe acute respiratory infections, we show that activation of epidermal and platelet-derived growth factor pathways are distinct features of COVID-19, deepening translational understanding of mechanisms potentially underlying SARS-CoV-2-associated pulmonary fibrosis. Collectively, our findings provide biological rationale for use of broad and targeted immunotherapies for severe COVID-19 in sub-Saharan Africa, illustrate the relevance of local viral and host factors to SARS-CoV-2 immunopathology, and highlight underemphasized yet therapeutically exploitable immune pathways driving COVID-19 severity. Less is known about SARS-CoV-2 infection in unstudied geographical areas such as sub-Saharan Africa. Here the authors use multi-omics to characterize the immune response to SARS-CoV-2 in Uganda and consider how people living with HIV immunologically differentially respond to the virus.
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    Descriptive epidemiology of rubella disease and associated virus strains in Uganda
    (Journal of Medical Virology, 2020) Tushabe, Phionah; Bwogi, Josephine; Abernathy, Emily; Birungi, Molly; Eliku, James P.; Seguya, Ronald; Bukenya, Henry; Namuwulya, Prossy; Kakooza, Proscovia; Suppiah, Suganthi; Kabaliisa, Theopista; Tibanagwa, Mayi; Ampaire, Immaculate; Kisakye, Annet; Bakainaga, Andrew; Byabamazima, Charles R.; Icenogle, Joseph P.; Bakamutumaho, Barnabas
    Rubella virus causes a mild disease; however, infection during the first trimester of pregnancy may lead to congenital rubella syndrome (CRS) in over 80% of affected pregnancies. Vaccination is recommended and has been shown to effectively reduce CRS incidence. Uganda plans to introduce routine rubella vaccination in 2019. The World Health Organization recommends assessing the disease burden and obtaining the baseline molecular virological data before vaccine introduction. Sera collected during case‐based measles surveillance from January 2005 to July 2018 were tested for rubella immunoglobulin M (IgM) antibodies. Sera from confirmed rubella outbreaks from January 2012 to August 2017 were screened using real‐time reverse‐transcription polymerase chain reaction (RT‐PCR); for positive samples, a region within the E1 glycoprotein coding region was amplified and sequenced. Of the 23 196 suspected measles cases serologically tested in parallel for measles and rubella, 5334 (23%) were rubella IgM‐positive of which 2710 (50.8%) cases were females with 2609 (96.3%) below 15 years of age. Rubella IgM‐positive cases were distributed throughout the country and the highest number was detected in April, August, and November. Eighteen (18%) of the 100 sera screened were real‐time RTPCR‐ positive of which eight (44.4%) were successfully sequenced and genotypes 1G and 2B were identified. This study reports on the seroprevalence and molecular epidemiology of rubella. Increased knowledge of former and current rubella viruses circulating in Uganda will enhance efforts to monitor the impact of vaccination as Uganda moves toward control and elimination of rubella and CRS.
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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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    Emerging epidemic of iatrogenic Acute Flaccid Paralysis in children under 15 years in Uganda
    (Pan African Medical Journal, 2012) Kisakye, Annet; Ndungutse, David; Byarugaba, Justus; Naddumba, Edward.K.; Mbabazi, William; Bakamutumaho, Barnabas; Bwogi, Josephine; Bakainaga, Andrew; Seruyange, Rachel; Mwesigye, Innocent; Ndugwa, Christopher M.
    Poliomyelitis a differential diagnosis of Acute Flaccid Paralysis (AFP) is a major disability. The prevalence of AFP associated with an intramuscular gluteal injection (s) among children below 15 years of age with fever reported through the AFP surveillance system between 2002 and 2008 in Uganda was studied. Methods A cross sectional study using AFP surveillance data. Any child aged below 15 years, who developed sudden flaccid paralysis between 1st January 2002 and 31st December 2008 was enrolled. NPEC conducted a desk review of completed AFP investigation forms for final classification. A case of an Injection Related Paralysis was defined as sudden onset of flaccid paralysis setting in within 72 hours of receipt of a gluteal intramuscular injection.
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    Hepatitis B infection is highly endemic in Uganda: findings from a national serosurvey
    (African health sciences, 2009) Bwogi, Josephine; Braka, Fiona; Makumbi, Issa; Mishra, Vinod; Bakamutumaho, Barnabas; Nanyunja, Miriam; Opio, Alex; Downing, Robert; Biryahwaho, Benon; Lewis, Rosamund F.
    Infant immunization against hepatitis B began in Uganda in 2002. Objective: To determine the baseline prevalence of hepatitis B virus (HBV) infection and explore risk factors. Methods: A hepatitis B prevalence study was nested in the 2005 national HIV/AIDS serobehavioural survey. Demographic characteristics and risk factors were explored by questionnaire. One third of blood specimens (n=5875) from adults aged 15 to 59 years were tested for hepatitis B core antibodies (HBcAb); positive specimens were tested for hepatitis B surface antigen (HBsAg). Results: HBcAb was present in 52.3% (95% CI: 51.0-53.6) of adults, and HBsAg in 10.3% (9.5-11.1). By 15-19 years of age, 40.0% had been infected with HBV. Prevalence of both markers was significantly higher across northern Uganda, in rural areas, among the poor and least educated, and in uncircumcised men. Other independent predictors of infection were age, ethnic group, occupation, number of sex partners, and HIV and HSV-2 status. Conclusion: Hepatitis B virus infection is highly endemic in Uganda, with transmission occurring in childhood and adulthood. More than 1.4 million adults are chronically infected and some communities disproportionately affected. The hepatitis B infant immunization programme should be sustained and catch-up vaccination considered for older children.
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    Molecular characterization of non‐polio enteroviruses isolated from acute flaccid paralysis patients in Uganda
    (Journal of Medical Virology, 2021) Tushabe, Phionah; Howard, Wayne; Bwogi, Josephine; Birungi, Molly; Eliku, James P.; Kakooza, Proscovia; Bukenya, Henry; Namuwulya, Prossy; Gaizi, Joseph; Tibanagwa, Mayi; Kabaliisa, Theopista; Mulindwa, Julius; Muhanguzi, Dennis; Suchard, Melinda; Gumede, Nicksy; Bakamutumaho, Barnabas
    Enteroviruses (EVs) are RNA viruses that can cause many clinical syndromes including acute flaccid paralysis (AFP). Within the global polio laboratory network, EVs are categorized either as polioviruses or non‐polio enteroviruses (NPEVs). Specific NPEVs have been described in polio‐like residual paralytic events in AFP patients. Retrospective analysis of 112 NPEV isolates from AFP patients was performed and thirty one NPEV types were identified of which 91% were Enterovirus B and 9% were Enterovirus A species. The NPEVs were distributed across the country with most patients in the eastern region (41/89; 46.1%). The highest proportion of patients were children less than 5 years (77/89; 86.5%) and male patients were more common (54/89; 60.7%). Echovirus 11 (11/89; 12.4%) was frequently observed and phylogenetic analysis of these sequences revealed high diversity. Coxsackievirus B5 (CV‐B5), CV‐B6, E21, and EV‐B69 were only seen in patients with residual paralysis. Analyses of the EV‐A71 sequence indicated a unique genogroup.
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    Phylogenetic Analysis of Rubella Viruses Identified in Uganda, 2003–2012
    (Journal of medical virology, 2014) Namuwulya, Prossy; Abernathy, Emily; Bukenya, Henry; Bwogi, Josephine; Tushabe, Phionah; Birungi, Molly; Seguya, Ronald; Kabaliisa, Theopista; Alibu, Vincent P.; Kayondo, Jonathan K.; Rivailler, Pierre; Icenogle, Joseph; Bakamutumaho, Barnabas
    Molecular data on rubella viruses are limited in Uganda despite the importance of congenital rubella syndrome (CRS). Routine rubella vaccination, while not administered currently in Uganda, is expected to begin by 2015. The World Health Organization recommends that countries without rubella vaccination programs assess the burden of rubella and CRS before starting a routine vaccination program. Uganda is already involved in integrated case-based surveillance, including laboratory testing to confirm measles and rubella, but molecular epidemiologic aspects of rubella circulation have so far not been documented in Uganda. Twenty throat swab or oral fluid samples collected from 12 districts during routine rash and fever surveillance between 2003 and 2012 were identified as rubella virus RNA positive and PCR products encompassing the region used for genotyping were sequenced. Phylogenetic analysis of the 20 sequences identified 19 genotype 1G viruses and 1 genotype 1E virus. Genotype-specific trees showed that the Uganda viruses belonged to specific clusters for both genotypes 1G and 1E and grouped with similar sequences from neighboring countries. Genotype 1G was predominant in Uganda. More epidemiological and molecular epidemiological data are required to determine if genotype 1E is also endemic in Uganda. The information obtained in this study will assist the immunization program in monitoring changes in circulating genotypes.
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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.