NRU :: Browsing by Author "Luboobi, Livingstone S."

Browsing by Author "Luboobi, Livingstone S."

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HIV Drug Resistance: Insights From Mathematical Modelling
(Applied Mathematical Modelling, 2019) Ngina, Purity; Mbogo, Rachel Waema; Luboobi, Livingstone S.
In 2013 the World Health Organization recommended the initiation of antiretroviral ther- apy (ART) to any person who tests HIV positive irrespective of his/her CD4 + count. How- ever, implementation of the new guidelines poses a lot of challenges especially in Sub- Sahara Africa such as: drug side effects, drug resistance-mutations and significant financial burdens. Most importantly, it has been established that HIV resistance and subsequent vi- rologic failure occur in a substantial proportion of HIV-infected patients receiving HAART. This study therefore, seeks to investigate the emergence of drug resistant HIV virus during treatment with the aim of determining the proper use of HIV therapy that would lessen drug resistance. To carry out the analysis a ten dimensional in-vivo mathematical model is proposed for HIV dynamics. The model is formulated in such away that it takes into account two virus strain, that is, the wild type as well as the naive type HIV virus. The in-vivo model is shown to be both biologically meaningful and mathematically well posed. The existence of unique infection-free equilibrium point is determined and both its local and global stability investigated. In addition, the basic reproduction number for each viral strain is computed using the next generation matrix method. An optimal control model is proposed and analysed by applying Pontryagin maximum principle, to obtain the op- timal drug combination for HIV treatment. Here two drugs, that is, Reverse Transcriptase inhibitor and Protease inhibitor are used as the controls in the model. We provide an ob- jective function for the minimisation of the number of wild type HIV virus and the drug resistant virus as well as the costs associated with the use of Reverse Transcriptase in- hibitor and protease inhibitor. The forward backward sweep method is applied to numer- ically solve the optimality system. From the numerical simulations, it is evident that pro- tease inhibitor is the most effective drug in controlling HIV infection. The results suggest that prolonged use of HAART leads to development of drug resistant and that people with drug-resistant infection could play a core role in the epidemic of HIV.
An HIV/AIDS Model With Variable Force Of Infection And Its Application To The Epidemic In Uganda
(American Journal of Applied Sciences, 2005) Baryarama, Flugentius; Mugisha, Joseph Y.T.; Luboobi, Livingstone S.
An HIV/AIDS model is formulated with variable force of infection for the adult population. Its actions are reduced to a prevalence equation that is a non-logistic equation whose explicit solution is derived. The implications of applying the solution to the evolution of the HIV/AIDS epidemic are discussed with respect to the positive boundedness of the coefficients. Prevalence projections are presented for various initial prevalences and behavior change parameters. The main finding is that in settings with high recruitment rates, the HIV epidemic reaches peak prevalence (and thereafter start declining) when the rate of new infections is still higher than the rate of removal of those infected with HIV.
A Mathematical Model Approach for Prevention and Intervention Measures of the COVID19 Pandemic in Uganda
(BMJ, 2020) Mbabazi, Fulgensia Kamugisha; Gavamukulya, Yahaya; Awichi, Richard; Olupot, Peter Olupot; Rwahwire, Samson; Biira, Saphina; Luboobi, Livingstone S.
The human–infecting corona virus disease (COVID–19) caused by the novel severe acute respiratory syndrome corona virus 2 (SARS–CoV–2) was declared a global pandemic on March 11th, 2020. Current human deaths due to the infection have raised the threat globally with only 1 African country free of Virus (Lesotho) as of May 6th, 2020. Different countries have adopted different interventions at different stages of the outbreak, with social distancing being the first option while lock down the preferred option for flattening the curve at the peak of the pandemic. Lock down is aimed at adherence to social distancing, preserve the health system and improve survival. We propose a Susceptible–Exposed–Infected–Expected recoveries (SEIR) mathematical model to study the impact of a variety of prevention and control strategies Uganda has applied since the eruption of the pandemic in the country. We analyze the model using available data to find the infection–free, endemic/infection steady states and the basic reproduction number. In addition, a sensitivity analysis done shows that the transmission rate and the rate at which persons acquire the virus, have a positive influence on the basic reproduction number. On other hand the rate of evacuation by rescue ambulance greatly reduces the reproduction number. The results have potential to inform the impact and effect of early strict interventions including lock down in resource limited settings and social distancing.
A Mathematical Model Approach for Prevention and Intervention Measures of the COVID{19 Pandemic in Uganda
(Asian Research Journal of Mathematics, 2022) Kamugisha Mbabazi, Fulgensia; Gavamukulya, Yahaya; Awichi, Richard; Olupot-Olupot, Peter; Rwahwire, Samson; Biira, Saphina; Luboobi, Livingstone S.
The human{infecting corona virus disease (COVID{19) caused by the novel severe acute respiratory syndrome corona virus 2 (SARS{CoV{2) was declared a global pandemic on March 11th, 2020. Current human deaths due to the infection have raised the threat globally with only 1 African country free of Virus (Lesotho) as of May 6th, 2020. Different countries have adopted different interventions at different stages of the outbreak, with social distancing being the first option while lock down the preferred option for flattening the curve at the peak of the pandemic. Lock down is aimed at adherence to social distancing, preserve the health system and improve survival. We propose a Susceptible{Exposed{Infected{Expected recoveries (SEIR) mathematical model to study the impact of a variety of prevention and control strategies Uganda has applied since the eruption of the pandemic in the country. We analyze the model using available data to find the infection{free, endemic/infection steady states and the basic reproduction number. In addition, a sensitivity analysis done shows that the transmission rate and the rate at which persons acquire the virus, have a positive influence on the basic reproduction number. On other hand the rate of evacuation by rescue ambulance greatly reduces the reproduction number. The results have potential to inform the impact and effect of early strict interventions including lock down in resource limited settings and social distancing.
A Mathematical Model for the Dynamics and Cost Effectiveness of the Current Controls of Cassava Brown Streak Disease in Uganda1
(J. Math. Comput. Sci, 2015) Kinene, Tonny; Luboobi, Livingstone S.; Nannyonga, Betty; Mwanga, Gasper G.
In this paper, Cassava brown streak disease (CBSD), transmitted from white fly vector to the host plant and vice versa, is a major threat to cassava production in Uganda and other cassava growing countries in Africa, e.g. Kenya, Tanzania, Malawi,Mozambique, e.t.c. The seriousness of the situation is that almost all varieties of cassava resistant to cassava mosaic disease (CMD) are susceptible to the new strain of CBSD. Numerous control measures are practiced by farmers, however, the cost effectiveness of these control measures have not been quantified. Therefore it is imperative that we formulate a mathematical model to investigate the transmission dynamics of CBSD and the cost-effectiveness of the control measures. In the analysis of the model we derived the basic reproduction number which helps us in establishing the stability of disease free and endemic equilibrium points. The model is then modified as an optimal control problem with an aim of minimizing the number of infected plants while keeping the cost low. Two time dependent controls are used in the model and an objective function which is a combination of the actual and relative costs associated with the controls is designed. Pontryagins Maximum Principle (PMP) is used to establish the necessary conditions for optimal control of the disease. The incremental cost-effectiveness ratio (ICER) is also computed and used to analyse the cost-effectiveness of the control strategies. Numerical results show that strategy B (uprooting and burning of infected plants) is cost effective, however if the government intervenes with massive spraying, strategy C (spraying with chemicals and uprooting and burning of infected plants) gives the farmer more yield.
A Mathematical Model For The Dynamics Of Malaria In A Human Host And Mosquito Vector With Temporary Immunity
(Applied Mathematics and Computation, 2007) Tumwiine, Julius; Mugisha, Joseph.Y.T.; Luboobi, Livingstone S.
In the paper, we propose a model that tracks the dynamics of malaria in the human host and mosquito vector. Our model incorporates some infected humans that recover from infection and immune humans after loss of immunity to the disease to join the susceptible class again. All the new borne are susceptible to the infection and there is no vertical transmission. The stability of the system is analyzed for the existence of the disease-free and endemic equilibria points. We established that the disease-free equilibrium point is globally asymptotically stable when the reproduction number, R0 6 1 and the disease always dies out. For R0 > 1 the disease-free equilibrium becomes unstable and the endemic equilibrium is globally asymptotically stable. Thus, due to new births and immunity loss to malaria, the susceptible class will always be refilled and the disease becomes more endemic.
Mathematical Modeling Of Liver Enzyme Elevation In HIV Mono-Infection
(Math Biosci., 2013) Nampala, Hasifa; Luboobi, Livingstone S.; Mugisha, Joseph Y.T.; Obua, Celestino
HIV-infected individuals are increasingly becoming susceptible to liver disease and, hence, liver-related mortality is on a rise. The presence of CD4+ in the liver and the presence of C-X-C chemokine receptor type 4 (CXCR4) on human hepatocytes provide a conducive environment for HIV invasion. In this study, a mathematical model is used to analyse the dynamics of HIV in the liver with the aim of investigating the existence of liver enzyme elevation in HIV mono-infected individuals. In the presence of HIV-specific cytotoxic T-lymphocytes, the model depicts a unique endemic equilibrium with a transcritical bifurcation when the basic reproductive number is unity. Results of the study show that the level of liver enzyme alanine aminotransferase (ALT) increases with increase in the rate of hepatocytes production. Numerical simulations reveal significant elevation of alanine aminotransferase with increase in viral load. The findings presuppose that while liver damage in HIV infection has mostly been associated with HIV/HBV coinfection and use of antiretroviral therapy (ART), it is possible to have liver damage solely with HIV infection.
Mathematical Modelling Of The In-Host Dynamics Of Malaria And The Effects Of Treatment
(Journal of Mathematics and Computer Science, 2017) Tabo, Zadoki; Luboobi, Livingstone S.; Ssebuliba, Joseph
Malaria research and mathematical models have mainly concentrated on malaria Plasmodium at the blood stage. This has left many questions concerning models of parasite dynamics in the liver and within the mosquito. These concerns are anticipated to keep scientists busy trying to understand the biology of the parasite for some more years to come. Thorough knowledge of parasite biology helps in designing appropriate drugs targeting particular stages of Plasmodium. To achieve this, there is need to study the transmission dynamics of malaria and the interaction between the infection in the liver, blood and mosquito using a mathematical model. In this study, a within-host mathematical model is proposed and considers the dynamics of P. falciparum malaria from the liver to the blood in the human host and then to the mosquito. Several techniques, including center manifold theory and sensitivity analysis are used to understand relevant features of the model dynamics like basic reproduction number, local and global stability of the disease-free equilibrium and conditions for existence of the endemic equilibrium. Results indicate that the infection rate of merozoites, the rate of sexual reproduction in gametocytes, burst size of both hepatocytes and erythrocytes are more sensitive parameters for the onset of the disease. However, a treatment strategy using highly effective drugs against such parameters can reduce on malaria progression and control the disease. Numerical simulations show that drugs with an efficacy above 90% boost healthy cells, reduce infected cells and clear parasites in human host. Therefore more needs to be done such as research in parasite biology and using highly effective drugs for treatment of malaria.
Modelling hepatotoxicity and antiretroviral therapeutic effect in HIV/HBV coinfection
(Elsevier, 2018) Luboobi, Livingstone S.; Nampala, Hasifa; Mugisha, Joseph Y.T.; Obua, Celestino; Sabuka, Matylda Jablonska
Enzyme alanine aminotransferase (ALT) elevation which reflects hepatocellular injury is a current challenge in people infected with human immunodeficiency virus (HIV) on antiretroviral therapy (ART). One of the factors that enhance the risk of hepatotoxicity is underlying diseases such as hepatitis caused by hepatitis B virus (HBV). HIV/HBV coinfected patients stand a greater risk of hepatotoxicity because all ART are toxic and liver cells (hepatocytes) that are responsible for metabolising the toxic ART, support all stages of HIV and HBV viral production. Mathematical models coupled with numerical simulations are used in this study with the aim of investigating the optimal combination of ART in HIV/HBV coinfection. Emtricitabine, tenofovir and efavirenz is the optimal combination that maximises the therapeutic effect of therapy and minimises the toxic response to medication in HIV/HBV coinfection.
Optimal Control Strategies For The Dynamics Of Rift Valley Fever
(Communications in Optimization Theory, 2014) Mpeshe, Saul C.; Luboobi, Livingstone S.; Nkansah-Gyekye, Yaw
A model to assess the impact of some control measures in the dynamics of Rift Valley Fever (RVF) is considered. We derived and analysed the conditions for optimal control of RVF with insecticides, vaccination, and personal protection using optimal control theory. We show that the control measures have a very desirable effect for reducing the number of infected individuals and that multiple controls are more effective than single control. Moreover, we show that effective and optimal use of insecticides and personal protection without the use of vaccination is not beneficial if total elimination of the disease is desirable in the community.
Optimal Control Techniques on a Mathematical Model for the Dynamics of Tungiasis in a Community
(International Journal of Mathematics and Mathematical Sciences, 2017) Kahuru, Jairos; Luboobi, Livingstone S.; Nkansah-Gyekye, Yaw
Tungiasis is a permanent penetration of female sand flea “Tunga penetrans” into the epidermis of its host. It affects human beings and domestic and sylvatic animals. In this paper, we apply optimal control techniques to a Tungiasis controlled mathematical model to determine the optimal control strategy in order to minimize the number of infested humans, infested animals, and sand flea populations. In an attempt to reduce Tungiasis infestation in human population, the control strategies based on personal protection, personal treatment, educational campaign, environmental sanitation, and insecticidal treatments on the affected parts as well as on animal fur are considered. We prove the existence of optimal control problem, determine the necessary conditions for optimality, and then perform numerical simulations. The numerical results showed that the control strategy comprises all five control measures and that which involves the three control measures of insecticide control, insecticidal dusting on animal furs, and environmental hygiene has the significant impact on Tungiasis transmission. Therefore, fighting against Tungiasis infestation in endemic settings, multidimensional control process should be employed in order to achieve the maximum benefits.
Periodicity of the HIV/AIDS Epidemic in a Mathematical Model that Incorporates Complacency
(American Journal of Infectious Diseases, 2005) Baryarama, Flugentius; Luboobi, Livingstone S.; Mugisha, Joseph Y.T.
An HIV/AIDS model incorporating complacency for the adult population is formulated. Complacency is assumed a function of the number of AIDS cases in a community with an inverse relation. A method to find the equilibrium state of the model is given by proving a stated theorem. An example to illustrate the application of the theorem is also given. Model analysis and simulations show that complacency resulting from dependence of HIV transmission on the number of AIDS cases in a community leads to damped periodic oscillations in the number of infective with oscillations more marked at lower rates of progression to AIDS. The implications of these results to public health with respect to monitoring the HIV/AIDS epidemic and widespread use of antiretroviral (ARV) drugs is discussed.
Recombination detected in the Heat Shock Protein 90 (HSP90) of the Bemisia tabaci species complex
(bioRxiv, 2019) Kinene, Tonny; Rossito De Marchi, Bruno; Alicai, Titus; Luboobi, Livingstone S.; Abu Omongo, Christopher; Savill, Anders; Boykin, Laura M.
Bemisia tabaci (whiteflies) are a global insect pest causing billions of dollars in damage each year, leaving farmers with low yields. In East Africa, whiteflies are superabundant and present on cassava plants throughout the year. Whiteflies do not decrease in number in the hot dry seasons in East Africa, therefore, it has been suggested that the synthesis of Heat Shock Protein (HSP) may protect the whitefly from heat stress and other biotic factors. In this study we used data sequence generated from individual whiteflies to assess variability and recombination of the HSP90 gene in members of the B. tabaci species complex. Results A total of 21 samples were sequenced on Illumina Hiseq 2500 and Hiseq 4000. These included eight genetic groups of B. tabaci: 7 SSA1, 5 SSA2, 2 Australia I (AUSI), 2 New World Africa (NWAfrica), B. afer, Uganda, Mediterranean (MED), and Middle East Asia Minor 1 (MEAM1). An alignment of 21 HSP90 sequences was generated after mapping and de novo assembly. Recombination analysis was performed on an alignment of 27 HSP90 sequences (we added an additional 6 sequences from GenBank). There were 18 recombination events detected in the HSP90 gene of the B. tabaci species complex, 7 of which were regarded as events that could be caused by evolutionary mechanisms such as gene duplication other than recombination. The phylogenetic analysis carried out on dataset without recombination events revealed a tree pattern with short terminal branches. Conclusion Recombination events were detected for members of the B. tabaci species complex in the HSP90 gene. This could explain the variability in the HSP90 gene of the B. tabaci species complex and highlight the phenomenon of the increased chance of survival and reproductive abundance of whiteflies in hot conditions in East Africa, since recombination is a major driving force of evolution.
Stochastic Model for Langerhans Cells and HIV Dynamics In Vivo
(International Scholarly Research Notice, 2014) Mbogo, Waema R.; Luboobi, Livingstone S.; Odhiambo, John.W.
Many aspects of the complex interaction between HIV and the human immune system remain elusive. Our objective is to study these interactions, focusing on the specific roles of Langerhans cells (LCs) in HIV infection. In patients infected with HIV, a large amount of virus is associated with LCs in lymphoid tissue. To assess the influence of LCs on HIV viral dynamics during antiretroviral therapy, we present and analyse a stochastic model describing the dynamics of HIV, CD+4 T cells, and LCs interactions under therapeutic intervention in vivo and show that LCs play an important role in enhancing and spreading initial HIV infection. We perform sensitivity analyses on the model to determine which parameters and/or which interaction mechanisms strongly affect infection dynamics.

Browsing by Author "Luboobi, Livingstone S."

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