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Article ; Online: Improving Outcomes for ARDS in Sub-Saharan Africa: The Time Is Now.

Cummings, Matthew J / Bakamutumaho, Barnabas

2023 Volume 164, Issue 2, Page(s) 275–277

MeSH term(s)	Humans ; Africa South of the Sahara/epidemiology ; Respiratory Distress Syndrome/therapy
Language	English
Publishing date	2023-08-09
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	1032552-9
ISSN	1931-3543 ; 0012-3692
ISSN (online)	1931-3543
ISSN	0012-3692
DOI	10.1016/j.chest.2023.03.017
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Article ; Online: The road to a polio-free Uganda; contribution of the Expanded Program on Immunization Laboratory (EPI-LAB) at Uganda Virus Research Institute.

Nanteza, Mary B / Tushabe, Phionah / Bukenya, Henry / Namuwulya, Prossy / Kabaliisa, Theopista / Birungi, Molly / Tibanagwa, Mayi / Ampeire, Immaculate / Kakooza, Proscovia / Katushabe, Edson / Bwogi, Josephine / Bakamutumaho, Barnabas / Nanyunja, Miriam / Byabamazima, Charles R

African health sciences

2024 Volume 23, Issue 3, Page(s) 186–196

Abstract: Background: The control of poliomyelitis in Uganda dates back as far as 1950 and acute flaccid paralysis (AFP) surveillance has since been used as a criterion for identifying wild polioviruses. Poliovirus isolation was initially pursued through ... ...

Abstract	Background: The control of poliomyelitis in Uganda dates back as far as 1950 and acute flaccid paralysis (AFP) surveillance has since been used as a criterion for identifying wild polioviruses. Poliovirus isolation was initially pursued through collaborative research however, in 1993, the Expanded Program on Immunization Laboratory (EPI-LAB) was established as a member of the Global Poliovirus Laboratory Network (GPLN) and spearheaded this activity at Uganda Virus Research Institute. Objectives: The aim of this report is to document the progress and impact of the EPI-LAB on poliovirus eradication in Uganda. Methods: Poliovirus detection and identification were achieved fundamentally through tissue culture and intra-typic differentiation of the poliovirus based on the real-time reverse transcriptase polymerase chain reaction (rRT PCR). The data obtained was entered into the national AFP database and analysed using EpiInfo Results: Quantitative and qualitative detection of wild and Sabin polioviruses corresponded with the polio campaigns. The WHO target indicators for AFP surveillance were achieved essentially throughout the study period. Conclusion: Virological tracking coupled with attaining standard AFP surveillance indicators has been pivotal in achieving and maintaining the national wild polio-free status. Laboratory surveillance remains key in informing the certification process of polio eradication.
MeSH term(s)	Humans ; Uganda/epidemiology ; alpha-Fetoproteins ; Population Surveillance ; Poliomyelitis/epidemiology ; Poliomyelitis/prevention & control ; Poliovirus/genetics ; Immunization
Chemical Substances	alpha-Fetoproteins
Language	English
Publishing date	2024-02-15
Publishing country	Uganda
Document type	Journal Article
ZDB-ID	2240308-5
ISSN	1729-0503 ; 1680-6905
ISSN (online)	1729-0503
ISSN	1680-6905
DOI	10.4314/ahs.v23i3.23
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Article ; Online: Shifting transmission patterns of human mpox in South Kivu, DR Congo.

Katoto, Patrick Dmc / Muttamba, Winters / Bahizire, Esto / Malembaka, Espoir Bwenge / Bosa, Henry Kyobe / Kazadi, Dieudonné Mwamba / Lubambo, Gaston / Siangoli, Freddy Belesi / Bakamutumaho, Barnabas / Wayengera, Misaki / Mavungu Landu, Don Jethro / Mukadi-Bamuleka, Daniel / Mbala, Placide / Loeb, Mark / Kirenga, Bruce / Muyembe-Tamfum, Jean-Jacques

The Lancet. Infectious diseases

2024

Language	English
Publishing date	2024-05-01
Publishing country	United States
Document type	Letter
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(24)00287-1
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Article ; Online: Rubella virus genotype 2B endemicity and related utility of serum-based molecular characterization in Uganda.

Tushabe, Phionah / Bakamutumaho, Barnabas / Eliku, James Peter / Birungi, Molly / Aine, Francis / Namuwulya, Prossy / Bukenya, Henry / Ampeire, Immaculate / Kisakye, Annet / Byabamazima, Charles R / Bwogi, Josephine

BMC research notes

2023 Volume 16, Issue 1, Page(s) 218

Abstract: There are 13 globally recognized rubella virus genotypes of which only 2 (1E and 2B) have been detected recently. The largest percentage of all reported rubella virus sequences come from China and Japan with Africa reporting limited data. In a bid to ... ...

Abstract	There are 13 globally recognized rubella virus genotypes of which only 2 (1E and 2B) have been detected recently. The largest percentage of all reported rubella virus sequences come from China and Japan with Africa reporting limited data. In a bid to address the lack of rubella genotype data in Uganda and the World Health Organization Africa region, we sought to characterize rubella viruses retrospectively using sera collected from suspected measles patients that turned out rubella IgM positive.Seven sequences belonging to genotype 2B sub-lineage 2B-L2c were obtained. These sequences clustered with other genotype 2B sequences previously reported from Uganda. None of the other genotypes (1E and 1G) reported from Uganda in the earlier years were detected. In addition, none of the sequences were obtained after the introduction of the measles-rubella containing vaccine. The above highlight the need for continuous rubella virological surveillance to confirm interruption of endemic rubella genotype circulation.
MeSH term(s)	Humans ; Rubella virus/genetics ; Uganda/epidemiology ; Retrospective Studies ; Rubella/epidemiology ; Genotype ; Measles/epidemiology ; Measles Vaccine
Chemical Substances	Measles Vaccine
Language	English
Publishing date	2023-09-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2413336-X
ISSN	1756-0500 ; 1756-0500
ISSN (online)	1756-0500
ISSN	1756-0500
DOI	10.1186/s13104-023-06499-5
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Article ; Online: Development of a Novel Clinicomolecular Risk Index to Enhance Mortality Prediction and Immunological Stratification of Adults Hospitalized with Sepsis in Sub-Saharan Africa: A Pilot Study from Uganda.

Cummings, Matthew J / Bakamutumaho, Barnabas / Jain, Komal / Price, Adam / Owor, Nicholas / Kayiwa, John / Namulondo, Joyce / Byaruhanga, Timothy / Muwanga, Moses / Nsereko, Christopher / Sameroff, Stephen / Ian Lipkin, W / Lutwama, Julius J / O'Donnell, Max R

The American journal of tropical medicine and hygiene

2023 Volume 108, Issue 3, Page(s) 619–626

Abstract: The global burden of sepsis is concentrated in sub-Saharan Africa (SSA), where epidemic HIV and unique pathogen diversity challenge the effective management of severe infections. In this context, patient stratification based on biomarkers of a ... ...

Abstract	The global burden of sepsis is concentrated in sub-Saharan Africa (SSA), where epidemic HIV and unique pathogen diversity challenge the effective management of severe infections. In this context, patient stratification based on biomarkers of a dysregulated host response may identify subgroups more likely to respond to targeted immunomodulatory therapeutics. In a prospective cohort of adults hospitalized with suspected sepsis in Uganda, we applied machine learning methods to develop a prediction model for 30-day mortality that integrates physiology-based risk scores with soluble biomarkers reflective of key domains of sepsis immunopathology. After model evaluation and internal validation, whole-blood RNA sequencing data were analyzed to compare biological pathway enrichment and inferred immune cell profiles between patients assigned differential model-based risks of mortality. Of 260 eligible adults (median age, 32 years; interquartile range, 26-43 years; 59.2% female, 53.9% living with HIV), 62 (23.8%) died by 30 days after hospital discharge. Among 14 biomarkers, soluble tumor necrosis factor receptor 1 (sTNFR1) and angiopoietin 2 (Ang-2) demonstrated the greatest importance for mortality prediction in machine learning models. A clinicomolecular model integrating sTNFR1 and Ang-2 with the Universal Vital Assessment (UVA) risk score optimized 30-day mortality prediction across multiple performance metrics. Patients assigned to the high-risk, UVA-based clinicomolecular subgroup exhibited a transcriptional profile defined by proinflammatory innate immune and necroptotic pathway activation, T-cell exhaustion, and expansion of key immune cell subsets including regulatory and gamma-delta T cells. Clinicomolecular stratification of adults with suspected sepsis in Uganda enhanced 30-day mortality prediction and identified a high-risk subgroup with a therapeutically targetable immunological profile. Further studies are needed to advance pathobiologically informed sepsis management in SSA.
MeSH term(s)	Humans ; Adult ; Female ; Male ; Pilot Projects ; Prospective Studies ; Uganda/epidemiology ; Sepsis ; Biomarkers ; HIV Infections/epidemiology
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-01-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
DOI	10.4269/ajtmh.22-0483
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Article ; Online: Sabin polio virus protein 1 (VP1) evolution in patients with acute flaccid paralysis from 2010 to 2016 in Uganda.

Nanteza, Mary Bridget / Bakamutumaho, Barnabas / Tushabe, Phionah / Namuwulya, Prossy / Birungi, Molly / Dhatemwa, Rajab / Eliku, James Peter / Tibanagwa, Mayi / Kakooza, Proscovia / Bukenya, Henry / Bwogi, Josephine / Byabamazima, Charles Rutebarika

Virology journal

2023 Volume 20, Issue 1, Page(s) 172

Abstract: Acute flaccid paralysis (AFP) is a rare side effect of the oral polio vaccine but can be associated with outbreaks and permanent disability in patients harboring circulating vaccine-derived polioviruses (cVDPVs). With the advancement of polio abolition ... ...

Abstract	Acute flaccid paralysis (AFP) is a rare side effect of the oral polio vaccine but can be associated with outbreaks and permanent disability in patients harboring circulating vaccine-derived polioviruses (cVDPVs). With the advancement of polio abolition in a glimpse, cVDPVs are causing outbreaks and slowing the polio eradication process. The polio virus protein 1 (VP1) contains the binding site that is key for virus transmission. Understanding the evolution of VP1 among AFP patients could yield more insight into the early events of cVDPVs. Polioviruses were identified from stool specimens of AFP patients using cell culture; and confirmed by the real time RT PCR intra-typic differentiation and vaccine-derived poliovirus assays. Seventy-nine (79) Sabin-like poliovirus 1 (SL1) and 86 Sabin-like poliovirus 3 (SL3) were sequenced. The VP1 amino acid substitutions T106A in Sabin poliovirus 1 and A54V in Sabin poliovirus 3 were common among the AFP patients as has been found in previous studies. Other substitutions that were associated with AFP were: T290A and A54T in SL1 and SL3 respectively. Nucleotide mutations that were common among the AFP patients included T402C, C670A, and T816C in SL1, and G22A, C375Y, A472R, and A694T in SL3 polioviruses. Characterizing mutations that are associated with AFP could contribute to efforts pursued to mitigate the risk of vaccine-derived polioviruses and promote development of safer vaccines.
MeSH term(s)	Humans ; Poliovirus/genetics ; Uganda/epidemiology ; alpha-Fetoproteins ; Enterovirus ; Poliomyelitis/epidemiology ; Poliomyelitis/prevention & control ; Poliovirus Vaccine, Oral/adverse effects ; Paralysis
Chemical Substances	alpha-Fetoproteins ; Poliovirus Vaccine, Oral
Language	English
Publishing date	2023-08-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2160640-7
ISSN	1743-422X ; 1743-422X
ISSN (online)	1743-422X
ISSN	1743-422X
DOI	10.1186/s12985-023-02143-7
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Article ; Online: Unfinished business: severe acute respiratory infection in sub-Saharan Africa.

Cummings, Matthew J / Bakamutumaho, Barnabas / O'Donnell, Max R

Intensive care medicine

2016 Volume 42, Issue 9, Page(s) 1515–1516

MeSH term(s)	Africa South of the Sahara ; Humans ; Respiratory Tract Infections
Language	English
Publishing date	2016-09
Publishing country	United States
Document type	Letter
ZDB-ID	80387-x
ISSN	1432-1238 ; 0340-0964 ; 0342-4642 ; 0935-1701
ISSN (online)	1432-1238
ISSN	0340-0964 ; 0342-4642 ; 0935-1701
DOI	10.1007/s00134-016-4383-7
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Article ; Online: COVID-19 immune signatures in Uganda persist in HIV co-infection and diverge by pandemic phase.

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 / Rwamutwe, Emmanuel / Nayiga, Irene / Kyebambe, Stephen / Haumba, Mercy / Bosa, Henry Kyobe / Ocom, Felix / Watyaba, Benjamin / Kikaire, Bernard /

Tomoiaga, Alin S / Kisaka, Stevens / Kiwanuka, Noah / Lipkin, W Ian / O'Donnell, Max R

Nature communications

2024 Volume 15, Issue 1, Page(s) 1475

Abstract: 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 ... ...

Abstract	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
MeSH term(s)	Adult ; Humans ; COVID-19 ; SARS-CoV-2 ; Coinfection/epidemiology ; Uganda/epidemiology ; Pandemics ; Prospective Studies ; HIV Infections/complications ; HIV Infections/epidemiology
Language	English
Publishing date	2024-02-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45204-3
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Article ; Online: Environmental surveillance detects circulating vaccine-derived poliovirus type 2 that was undetected by acute flaccid paralysis surveillance in 2021 in Uganda.

Tushabe, Phionah / Bwogi, Josephine / Eliku, James Peter / Aine, Francis / Birungi, Molly / Gaizi, Joseph / Nakabazzi, Lucy / Kabaliisa, Theopista / Turyahabwe, Irene / Namuwulya, Prossy / Nanteza, Mary Bridget / Bukenya, Henry / Kanyesigye, Christopher / Katushabe, Edson / Ampeire, Immaculate / Kisakye, Annet / Bakamutumaho, Barnabas / Byabamazima, Charles R

Archives of virology

2023 Volume 168, Issue 5, Page(s) 140

Abstract: The success of the global polio eradication initiative is threatened by the genetic instability of the oral polio vaccine, which can result in the emergence of pathogenic vaccine-derived polioviruses following prolonged replication in the guts of ... ...

Abstract	The success of the global polio eradication initiative is threatened by the genetic instability of the oral polio vaccine, which can result in the emergence of pathogenic vaccine-derived polioviruses following prolonged replication in the guts of individuals with primary immune deficiencies or in communities with low vaccination coverage. Through environmental surveillance, circulating vaccine-derived poliovirus type 2 was detected in Uganda in the absence of detection by acute flaccid paralysis (AFP) surveillance. This underscores the sensitivity of environmental surveillance and emphasizes its usefulness in supplementing AFP surveillance for poliovirus infections in the race towards global polio eradication.
MeSH term(s)	Humans ; alpha-Fetoproteins ; Environmental Monitoring ; Paralysis/epidemiology ; Paralysis/etiology ; Poliomyelitis/epidemiology ; Poliomyelitis/prevention & control ; Poliovirus/genetics ; Poliovirus Vaccine, Oral/adverse effects ; Population Surveillance ; Uganda/epidemiology
Chemical Substances	alpha-Fetoproteins ; Poliovirus Vaccine, Oral
Language	English
Publishing date	2023-04-15
Publishing country	Austria
Document type	Journal Article
ZDB-ID	7491-3
ISSN	1432-8798 ; 0304-8608
ISSN (online)	1432-8798
ISSN	0304-8608
DOI	10.1007/s00705-023-05759-w
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Article ; Online: A Transcriptomic Classifier Model Identifies High-Risk Endotypes in a Prospective Study of Sepsis in Uganda.

Cummings, Matthew J / Bakamutumaho, Barnabas / Tomoiaga, Alin S / Owor, Nicholas / Jain, Komal / Price, Adam / Kayiwa, John / Namulondo, Joyce / Byaruhanga, Timothy / Muwanga, Moses / Nsereko, Christopher / Nayiga, Irene / Kyebambe, Stephen / Sameroff, Stephen / Che, Xiaoyu / Lutwama, Julius J / Lipkin, W Ian / O'Donnell, Max R

Critical care medicine

2023 Volume 52, Issue 3, Page(s) 475–482

Abstract: Objectives: In high-income countries (HICs), sepsis endotypes defined by distinct pathobiological mechanisms, mortality risks, and responses to corticosteroid treatment have been identified using blood transcriptomics. The generalizability of these ... ...

Abstract	Objectives: In high-income countries (HICs), sepsis endotypes defined by distinct pathobiological mechanisms, mortality risks, and responses to corticosteroid treatment have been identified using blood transcriptomics. The generalizability of these endotypes to low-income and middle-income countries (LMICs), where the global sepsis burden is concentrated, is unknown. We sought to determine the prevalence, prognostic relevance, and immunopathological features of HIC-derived transcriptomic sepsis endotypes in sub-Saharan Africa. Design: Prospective cohort study. Setting: Public referral hospital in Uganda. Patients: Adults ( n = 128) hospitalized with suspected sepsis. Interventions: None. Measurements and main results: Using whole-blood RNA sequencing data, we applied 19-gene and 7-gene classifiers derived and validated in HICs (SepstratifieR) to assign patients to one of three sepsis response signatures (SRS). The 19-gene classifier assigned 30 (23.4%), 92 (71.9%), and 6 (4.7%) patients to SRS-1, SRS-2, and SRS-3, respectively, the latter of which is designed to capture individuals transcriptionally closest to health. SRS-1 was defined biologically by proinflammatory innate immune activation and suppressed natural killer-cell, T-cell, and B-cell immunity, whereas SRS-2 was characterized by dampened innate immune activation, preserved lymphocyte immunity, and suppressed transcriptional responses to corticosteroids. Patients assigned to SRS-1 were predominantly (80.0% [24/30]) persons living with HIV with advanced immunosuppression and frequent tuberculosis. Mortality at 30-days differed significantly by endotype and was highest (48.1%) in SRS-1. Agreement between 19-gene and 7-gene SRS assignments was poor (Cohen's kappa 0.11). Patient stratification was suboptimal using the 7-gene classifier with 15.1% (8/53) of individuals assigned to SRS-3 deceased at 30-days. Conclusions: Sepsis endotypes derived in HICs share biological and clinical features with those identified in sub-Saharan Africa, with major differences in host-pathogen profiles. Our findings highlight the importance of context-specific sepsis endotyping, the generalizability of conserved biological signatures of critical illness across disparate settings, and opportunities to develop more pathobiologically informed sepsis treatment strategies in LMICs.
MeSH term(s)	Adult ; Humans ; Transcriptome ; Prospective Studies ; Uganda/epidemiology ; Sepsis ; Gene Expression Profiling ; Adrenal Cortex Hormones
Chemical Substances	Adrenal Cortex Hormones
Language	English
Publishing date	2023-08-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0000000000006023
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