Rebecca Nsubuga | Makerere University (original) (raw)
Papers by Rebecca Nsubuga
Annual Review of Statistics and Its Application
Several major global challenges, including climate change and water scarcity, warrant a scientifi... more Several major global challenges, including climate change and water scarcity, warrant a scientific approach to generating solutions. Developing high quality and robust capacity in (bio)statistics is key to ensuring sound scientific solutions to these challenges, so collaboration between academic and research institutes should be high on university agendas. To strengthen capacity in the developing world, South–North partnerships should be a priority. The ideas and examples of statistical capacity-building presented in this article are the result of several monthly online discussions between a mixedgroup of authors having international experience and formal links with Hasselt University in Belgium. The discussion focuses on statistical capacity-building through education (teaching), research, and societal impact. We have adopted an example-based approach, and in view of the background of the authors, the examples refer mainly to biostatistical capacity-building. Although many universi...
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BMC Infectious Diseases, Aug 9, 2017
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Sexually Transmitted Infections, Jul 18, 2011
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F1000Research, Feb 15, 2017
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BMJ Global Health, 2017
S OF PLENARY PRESENTATIONS A3 ABSTRACTS OF ORAL PRESENTATIONS A5S OF ORAL PRESENTATIONS A5 ABSTRA... more S OF PLENARY PRESENTATIONS A3 ABSTRACTS OF ORAL PRESENTATIONS A5S OF ORAL PRESENTATIONS A5 ABSTRACTS OF POSTER PRESENTATIONS A16S OF POSTER PRESENTATIONS A16
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Virus Evolution, 2020
Recombination is an important feature of HIV evolution, occurring both within and between the maj... more Recombination is an important feature of HIV evolution, occurring both within and between the major branches of diversity (subtypes). The Ugandan epidemic is primarily composed of two subtypes, A1 and D, that have been co-circulating for 50 years, frequently recombining in dually infected patients. Here, we investigate the frequency of recombinants in this population and the location of breakpoints along the genome. As part of the PANGEA-HIV consortium, 1,472 consensus genome sequences over 5 kb have been obtained from 1,857 samples collected by the MRC/UVRI & LSHTM Research unit in Uganda, 465 (31.6 per cent) of which were near full-length sequences (>8 kb). Using the subtyping tool SCUEAL, we find that of the near full-length dataset, 233 (50.1 per cent) genomes contained only one subtype, 30.8 per cent A1 (n = 143), 17.6 per cent D (n = 82), and 1.7 per cent C (n = 8), while 49.9 per cent (n = 232) contained more than one subtype (including A1/D (n = 164), A1/C (n = 13), C/D (...
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Journal of Antimicrobial Chemotherapy, 2019
ObjectivesWe examined virological outcomes, patterns of acquired HIV drug resistance (ADR), corre... more ObjectivesWe examined virological outcomes, patterns of acquired HIV drug resistance (ADR), correlates of virological failure (VF) and acquired drug resistance among fisherfolk on first-line ART.MethodsWe enrolled 1169 adults on ART for a median duration of 6, 12, 24, 36 and ≥48 months and used a pooled VL testing approach to identify VF (VL ≥1000 copies/mL). We performed genotyping among VF cases and determined correlates of VF and ADR by logistic regression.ResultsThe overall virological suppression rate was 91.7% and ADR was detected in 71/97 (73.2%) VF cases. The most prevalent mutations were M184V/I (53.6%) for NRTIs and K103N (39.2%) for NNRTIs. Thymidine analogue mutations were detected in 21.6% of VF cases while PI mutations were absent. A zidovudine-based ART regimen, duration on ART (≥24 months) and secondary/higher education level were significantly associated with VF. A nevirapine-based regimen [adjusted OR (aOR): 1.87; 95% CI: 0.03–0.54)] and VL ≥10000 copies/mL (aOR: 3...
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Journal of Epidemiology and Community Health, Aug 1, 2011
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Genome-wide association studies (GWAS) for kidney function have uncovered hundreds of risk loci, ... more Genome-wide association studies (GWAS) for kidney function have uncovered hundreds of risk loci, primarily in populations of European ancestry. We conducted the first GWAS of estimated glomerular filtration rate (eGFR) in Africa in 3288 Ugandans and replicated the findings in 8224 African Americans. We identified two loci associated with eGFR at genome-wide significance (p<5×10−8). The most significantly associated variant (rs2433603, p=2.4×10−9) in GATM was distinct from previously reported signals. A second association signal mapping near HBB (rs141845179, p=3.0×10−8) was not significant after conditioning on a previously reported SNP (rs334) for eGFR. However, fine-mapping analyses highlighted rs141845179 to be the most likely causal variant at the HBB locus (posterior probability of 0.61). A trans-ethnic GRS of eGFR constructed from previously reported lead SNPs was not predictive into the Ugandan population, indicating that additional large-scale efforts in Africa are necess...
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Cell, 2019
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Frontiers in Genetics, 2021
Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolesce... more Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolescents are associated with poor disease outcomes, such as faster HIV disease progression. Although it has been suggested that the development of IMDs is moderated by interaction of stressful life events and vulnerability factors, the underlying etiology is largely unknown. Serotonin transporter gene [solute carrier family 6 member A4 (SLC6A4)] and human tryptophan hydroxylase 2 gene (TPH2) polymorphisms have been implicated in the development of IMDs. This study investigated the association between acute stress and IMDs, and moderation by chronic stress and genetic variants in SLC6A4 and TPH2.Hypothesis: Acute stress acts through genetic and environmental vulnerability factors to increase the risk of developing IMDs.Methods: Polymorphisms in SLC6A4 (5-HTTLPR, rs25531, 5-HTTLPR-rs25531, and STin2 VNTR) and TPH2 (rs1843809, rs1386494, rs4570625, and rs34517220) were genotyped in 368 HIV+ chil...
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BIOMATH
In this work, we formulated and analysed a deterministic model to study the HIV-HCV co-infection ... more In this work, we formulated and analysed a deterministic model to study the HIV-HCV co-infection dynamics in presence of HIV therapy. The HCV chronic stage was split into two periods: the period before and the period after onset of cirrhosis. This was done because the HCV chronic stage of infection is long, asymptomatic and infectious. The effective reproduction numbers, one of our outcome measures, were computed using the next generation matrix method. Numerical simulations were performed to support the analytical results from the model. The different parameters in the model were subjected to a sensitivity analysis to determine their relative importance on the HIV-HCV co-infection dynamics. The results indicated that both HIV and HCV infections enhance each other; and in the long run, increasing the rates at which people are put on HIV treatment reduces the prevalence of HCV in the community; however, it increases the prevalence of HIV. Therefore, there should be increased safer se...
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Computational and Mathematical Methods in Medicine, 2020
Globally, it is estimated that of the 36.7 million people infected with human immunodeficiency vi... more Globally, it is estimated that of the 36.7 million people infected with human immunodeficiency virus (HIV), 6.3% are coinfected with hepatitis C virus (HCV). Coinfection with HIV reduces the chance of HCV spontaneous clearance. In this work, we formulated and analysed a deterministic model to study the HIV and HCV coinfection dynamics in absence of therapy. Due to chronic stage of HCV infection being long, asymptomatic, and infectious, our model formulation was based on the splitting of the chronic stage into the following: before onset of cirrhosis and its complications and after onset of cirrhosis. We computed the basic reproduction numbers using the next generation matrix method. We performed numerical simulations to support the analytical results. We carried out sensitivity analysis to determine the relative importance of the different parameters influencing the HIV-HCV coinfection dynamics. The findings reveal that, in the long run, there is a substantial number of individuals ...
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Sexually Transmitted Infections, 2016
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Science (New York, N.Y.), Jan 11, 2016
Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholestero... more Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subj...
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AIDS, 2011
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Scientific Reports, 2019
Although fishing communities (FCs) in Uganda are disproportionately affected by HIV-1 relative to... more Although fishing communities (FCs) in Uganda are disproportionately affected by HIV-1 relative to the general population (GP), the transmission dynamics are not completely understood. We earlier found most HIV-1 transmissions to occur within FCs of Lake Victoria. Here, we test the hypothesis that HIV-1 transmission in FCs is isolated from networks in the GP. We used phylogeography to reconstruct the geospatial viral migration patterns in 8 FCs and 2 GP cohorts and a Bayesian phylogenetic inference in BEAST v1.8.4 to analyse the temporal dynamics of HIV-1 transmission. Subtype A1 (pol region) was most prevalent in the FCs (115, 45.1%) and GP (177, 50.4%). More recent HIV transmission pairs from FCs were found at a genetic distance (GD) <1.5% than in the GP (Fisher’s exact test, p = 0.001). The mean time depth for pairs was shorter in FCs (5 months) than in the GP (4 years). Phylogeographic analysis showed strong support for viral migration from the GP to FCs without evidence of su...
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Annual Review of Statistics and Its Application
Several major global challenges, including climate change and water scarcity, warrant a scientifi... more Several major global challenges, including climate change and water scarcity, warrant a scientific approach to generating solutions. Developing high quality and robust capacity in (bio)statistics is key to ensuring sound scientific solutions to these challenges, so collaboration between academic and research institutes should be high on university agendas. To strengthen capacity in the developing world, South–North partnerships should be a priority. The ideas and examples of statistical capacity-building presented in this article are the result of several monthly online discussions between a mixedgroup of authors having international experience and formal links with Hasselt University in Belgium. The discussion focuses on statistical capacity-building through education (teaching), research, and societal impact. We have adopted an example-based approach, and in view of the background of the authors, the examples refer mainly to biostatistical capacity-building. Although many universi...
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BMC Infectious Diseases, Aug 9, 2017
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Sexually Transmitted Infections, Jul 18, 2011
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F1000Research, Feb 15, 2017
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BMJ Global Health, 2017
S OF PLENARY PRESENTATIONS A3 ABSTRACTS OF ORAL PRESENTATIONS A5S OF ORAL PRESENTATIONS A5 ABSTRA... more S OF PLENARY PRESENTATIONS A3 ABSTRACTS OF ORAL PRESENTATIONS A5S OF ORAL PRESENTATIONS A5 ABSTRACTS OF POSTER PRESENTATIONS A16S OF POSTER PRESENTATIONS A16
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Virus Evolution, 2020
Recombination is an important feature of HIV evolution, occurring both within and between the maj... more Recombination is an important feature of HIV evolution, occurring both within and between the major branches of diversity (subtypes). The Ugandan epidemic is primarily composed of two subtypes, A1 and D, that have been co-circulating for 50 years, frequently recombining in dually infected patients. Here, we investigate the frequency of recombinants in this population and the location of breakpoints along the genome. As part of the PANGEA-HIV consortium, 1,472 consensus genome sequences over 5 kb have been obtained from 1,857 samples collected by the MRC/UVRI & LSHTM Research unit in Uganda, 465 (31.6 per cent) of which were near full-length sequences (>8 kb). Using the subtyping tool SCUEAL, we find that of the near full-length dataset, 233 (50.1 per cent) genomes contained only one subtype, 30.8 per cent A1 (n = 143), 17.6 per cent D (n = 82), and 1.7 per cent C (n = 8), while 49.9 per cent (n = 232) contained more than one subtype (including A1/D (n = 164), A1/C (n = 13), C/D (...
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Journal of Antimicrobial Chemotherapy, 2019
ObjectivesWe examined virological outcomes, patterns of acquired HIV drug resistance (ADR), corre... more ObjectivesWe examined virological outcomes, patterns of acquired HIV drug resistance (ADR), correlates of virological failure (VF) and acquired drug resistance among fisherfolk on first-line ART.MethodsWe enrolled 1169 adults on ART for a median duration of 6, 12, 24, 36 and ≥48 months and used a pooled VL testing approach to identify VF (VL ≥1000 copies/mL). We performed genotyping among VF cases and determined correlates of VF and ADR by logistic regression.ResultsThe overall virological suppression rate was 91.7% and ADR was detected in 71/97 (73.2%) VF cases. The most prevalent mutations were M184V/I (53.6%) for NRTIs and K103N (39.2%) for NNRTIs. Thymidine analogue mutations were detected in 21.6% of VF cases while PI mutations were absent. A zidovudine-based ART regimen, duration on ART (≥24 months) and secondary/higher education level were significantly associated with VF. A nevirapine-based regimen [adjusted OR (aOR): 1.87; 95% CI: 0.03–0.54)] and VL ≥10000 copies/mL (aOR: 3...
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Journal of Epidemiology and Community Health, Aug 1, 2011
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Genome-wide association studies (GWAS) for kidney function have uncovered hundreds of risk loci, ... more Genome-wide association studies (GWAS) for kidney function have uncovered hundreds of risk loci, primarily in populations of European ancestry. We conducted the first GWAS of estimated glomerular filtration rate (eGFR) in Africa in 3288 Ugandans and replicated the findings in 8224 African Americans. We identified two loci associated with eGFR at genome-wide significance (p<5×10−8). The most significantly associated variant (rs2433603, p=2.4×10−9) in GATM was distinct from previously reported signals. A second association signal mapping near HBB (rs141845179, p=3.0×10−8) was not significant after conditioning on a previously reported SNP (rs334) for eGFR. However, fine-mapping analyses highlighted rs141845179 to be the most likely causal variant at the HBB locus (posterior probability of 0.61). A trans-ethnic GRS of eGFR constructed from previously reported lead SNPs was not predictive into the Ugandan population, indicating that additional large-scale efforts in Africa are necess...
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Cell, 2019
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Frontiers in Genetics, 2021
Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolesce... more Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolescents are associated with poor disease outcomes, such as faster HIV disease progression. Although it has been suggested that the development of IMDs is moderated by interaction of stressful life events and vulnerability factors, the underlying etiology is largely unknown. Serotonin transporter gene [solute carrier family 6 member A4 (SLC6A4)] and human tryptophan hydroxylase 2 gene (TPH2) polymorphisms have been implicated in the development of IMDs. This study investigated the association between acute stress and IMDs, and moderation by chronic stress and genetic variants in SLC6A4 and TPH2.Hypothesis: Acute stress acts through genetic and environmental vulnerability factors to increase the risk of developing IMDs.Methods: Polymorphisms in SLC6A4 (5-HTTLPR, rs25531, 5-HTTLPR-rs25531, and STin2 VNTR) and TPH2 (rs1843809, rs1386494, rs4570625, and rs34517220) were genotyped in 368 HIV+ chil...
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BIOMATH
In this work, we formulated and analysed a deterministic model to study the HIV-HCV co-infection ... more In this work, we formulated and analysed a deterministic model to study the HIV-HCV co-infection dynamics in presence of HIV therapy. The HCV chronic stage was split into two periods: the period before and the period after onset of cirrhosis. This was done because the HCV chronic stage of infection is long, asymptomatic and infectious. The effective reproduction numbers, one of our outcome measures, were computed using the next generation matrix method. Numerical simulations were performed to support the analytical results from the model. The different parameters in the model were subjected to a sensitivity analysis to determine their relative importance on the HIV-HCV co-infection dynamics. The results indicated that both HIV and HCV infections enhance each other; and in the long run, increasing the rates at which people are put on HIV treatment reduces the prevalence of HCV in the community; however, it increases the prevalence of HIV. Therefore, there should be increased safer se...
Bookmarks Related papers MentionsView impact
Computational and Mathematical Methods in Medicine, 2020
Globally, it is estimated that of the 36.7 million people infected with human immunodeficiency vi... more Globally, it is estimated that of the 36.7 million people infected with human immunodeficiency virus (HIV), 6.3% are coinfected with hepatitis C virus (HCV). Coinfection with HIV reduces the chance of HCV spontaneous clearance. In this work, we formulated and analysed a deterministic model to study the HIV and HCV coinfection dynamics in absence of therapy. Due to chronic stage of HCV infection being long, asymptomatic, and infectious, our model formulation was based on the splitting of the chronic stage into the following: before onset of cirrhosis and its complications and after onset of cirrhosis. We computed the basic reproduction numbers using the next generation matrix method. We performed numerical simulations to support the analytical results. We carried out sensitivity analysis to determine the relative importance of the different parameters influencing the HIV-HCV coinfection dynamics. The findings reveal that, in the long run, there is a substantial number of individuals ...
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Sexually Transmitted Infections, 2016
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Science (New York, N.Y.), Jan 11, 2016
Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholestero... more Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subj...
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
AIDS, 2011
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Scientific Reports, 2019
Although fishing communities (FCs) in Uganda are disproportionately affected by HIV-1 relative to... more Although fishing communities (FCs) in Uganda are disproportionately affected by HIV-1 relative to the general population (GP), the transmission dynamics are not completely understood. We earlier found most HIV-1 transmissions to occur within FCs of Lake Victoria. Here, we test the hypothesis that HIV-1 transmission in FCs is isolated from networks in the GP. We used phylogeography to reconstruct the geospatial viral migration patterns in 8 FCs and 2 GP cohorts and a Bayesian phylogenetic inference in BEAST v1.8.4 to analyse the temporal dynamics of HIV-1 transmission. Subtype A1 (pol region) was most prevalent in the FCs (115, 45.1%) and GP (177, 50.4%). More recent HIV transmission pairs from FCs were found at a genetic distance (GD) <1.5% than in the GP (Fisher’s exact test, p = 0.001). The mean time depth for pairs was shorter in FCs (5 months) than in the GP (4 years). Phylogeographic analysis showed strong support for viral migration from the GP to FCs without evidence of su...
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