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UFS PhD study focuses on improving life expectancy of HIV/Aids patients

11 December 2019 | Story Leonie Bolleurs

According to Global Statistics, there were approximately 37,9 million people across the globe with HIV/Aids in 2018. They also state that in 2018, an estimated 1,7 million individuals worldwide became newly infected with HIV.

In the city of Masvingo, Zimbabwe, Claris Shoko is a Statistics lecturer at the Great Zimbabwe University. In her PhD thesis at the University of the Free State (UFS) in the Department of Mathematical Statistics and Actuarial Sciences, she presented the argument that the inclusion of both the CD4 cell count and the viral-load counts in the monitoring and management of HIV+ patients on antiretroviral therapy (ART), is helping in reducing mortality rates, leading to improved life expectancy for HIV/Aids patients.

She received her doctoral degree at the December UFS Graduation Ceremonies, with her thesis: Continuous-time Markov modelling of the effects of treatment regimens on HIV/Aids immunology and virology.

CD4 cell count and viral-load count

Dr Shoko explains: “When the human immunodeficiency virus (HIV) enters the human body, the virus attacks the CD4 cells in their blood. This process damages CD4 cells, causing the number of white blood cells in the body to drop, making it difficult to fight infections.”

“Clinical markers such as CD4 cell count and viral-load count (number of HIV particles in a ml of blood) provide information about the progression of HIV/Aids in infected individuals. These markers fully define the immunology and the virology of HIV-infected individuals, thereby giving us a clear picture of how HIV/Aids evolve within an individual.”

Dr Shoko continues: “The development of highly active antiretroviral therapy (HAART) has helped substantially to reduce the death rate from HIV. HAART reduces viral load-count levels, blocking replication of HIV particles in the blood, resulting in an increase of CD4 cell counts and the life expectancy of individuals infected with HIV. This has made CD4 cell counts and viral-load counts the fundamental laboratory markers that are regularly used for patient management, in addition to predicting HIV/Aids disease progression or treatment outcomes.”

In the treatment of HIV/Aids, medical practitioners prescribe combination therapy to attack the virus at different stages of its life cycle, and medication to treat the opportunistic infections that may occur. “The introduction of combined antiretroviral therapy (cART) has led to the dramatic reduction in morbidity and mortality at both individual level and population level,” states Dr Shoko.

Once HIV-positive patients are put on cART, the effectiveness of treatment is monitored after the first three months and a further follow-up is done every six months thereafter. During the monitoring stages, CD4 cell count and viral load is measured. Patients are also screened for any tuberculosis (TB) co-infection and checked for any signs of drug resistance. These variables determine whether or not there is a need for treatment change.

She continues: “Previous studies on HIV modelling could not include both CD4 cell count and viral load in one model, because of the collinearity between the two variables. In this study, the principal component approach for the treatment of collinearity between variables is used. Both variables were then included in one model, resulting in a better prediction of mortality than when only one of the variables is used.”

“Viral-load monitoring helps in checking for any possibilities of virologic failure or viral rebound, which increases the rate of mortality if not managed properly. CD4 cell count then comes in to monitor the potential development of opportunistic infections such as TB. TB is extremely fatal, but once detected and treated, the survival of HIV/Aids patients is assured,” Dr Shoko explains.

Markov model

She applied the Markov model in her study. The model, named after the Russian mathematician Andrey Markov, represents a general category of stochastic processes, characterised by six basic attributes: states, stages, actions, rewards, transitions, and constraints.

According to Dr Shoko, Markov models assume that a patient is always in one of a finite number of discrete states, called Markov states. All events are modelled as transitions from one state to another. Each state is assigned a utility, and the contribution of this utility to the overall prognosis depends on the length of time spent in each state. For example, for a patient who is HIV positive, these states could be HIV+ (CD4 cell count above 200 cells/mm3), Aids (CD4 cell count below 200 cells/mm3) and Dead.

“Markov models are ideal for use in HIV/Aids studies, because they estimate the rate of transition between multiple-disease states while allowing for the possible reversibility of some states,” says Dr Shoko, quoting Hubbard and Zhou.

“Relatively fewer HIV modelling studies include a detailed description of the dynamics of HIV viral load count during stages of HIV disease progression. This could be due to the unavailability of data on viral load, particularly from low- and middle-income countries that have historically relied on monitoring CD4 cell counts for patients on ART because of higher costs of viral load-count testing,” Dr Shoko concludes

News Archive

Studies to reveal correlation between terrain, energy use, and giraffe locomotion

2016-11-18

More than half of giraffes in captivity in Europe are afflicted by lameness. This high prevalence represents an important welfare issue, similar to other large zoo animals.

According to Dr Chris Basu, a veterinarian at the Royal Veterinary College in the UK, giraffes in captivity are often afflicted by overgrown hooves, laminitis and joint problems. Diagnosis and treatment is limited by our understanding of anatomy and function, more specifically the locomotion of these animals. Although the giraffe is such a well-known and iconic animal, relatively little has been studied about their locomotor behaviour.

Dr Basu recently visited South Africa to do fieldwork on the locomotion of giraffes as part of his PhD studies under the mentorship of world-renowned Professor of Evolutionary Biomechanics, Prof John Hutchinson. This project is a joint venture between Dr Basu and Dr Francois Deacon, researcher in the Department of Animal, Wildlife, and Grassland Sciences at the UFS. Dr Deacon is a specialist in giraffe habitat-related research.

Together Prof Hutchinson and Drs Deacon and Basu form a research group, working on studies about giraffe locomotion.

Wild giraffe population decrease by 40% in past decade

“Locomotion is one of the most common animal behaviours and comes with a significant daily energetic cost. Studying locomotion of wild animals aids us in making estimates of this energetic cost. Such estimates are useful in understanding how giraffes fit into ecosystems. Future conservation efforts will be influenced by knowledge of the energy demands in giraffes.

“Understanding aspects of giraffe locomotion also helps us to understand the relationships between anatomy, function and evolution. This is relevant to our basic understanding of the natural world, as well as to conservation and veterinary issues,” said Dr Deacon.

Locomotion study brings strategy for specialist foot care

On face value it seems as if foot disease pathologies are more common in zoo giraffes than in wild giraffes. “However, we need a good sample of data from both populations to prove this assumption,” said Dr Basu.

This phenomenon is not well understood at the moment, but it’s thought that diet, substrate (e.g. concrete, straw, sand and grass) and genetics play a part in foot disease in giraffes. “Understanding how the feet are mechanically loaded during common activities (standing, walking, running) gives our research group ideas of where the highest strains occur, and later how these can be reduced through corrective foot trimming,” said Dr Basu.

Through the studies on giraffe locomotion, the research group plans to devise strategies for corrective foot trimming. At the moment, foot trimming is done with the best evidence available, which is extrapolation from closely related animals such as cattle. “But we know that giraffes’ specialist anatomy will likely demand specialist foot care,” Dr Basu said.

Studying giraffes in smaller versus larger spaces

The research group has begun to study the biomechanics of giraffe walking by looking at the kinematics (the movement) and the kinetics (the forces involved in movement) during walking strides. For this he studied adult giraffes at three zoological parks in the UK.

However, due to the close proximity of fencing and buildings, it is not practical to study fast speeds in a zoo setting.

A setting such as the Willem Pretorius Nature Reserve, near Ventersburg in the Free State, Kwaggafontein Nature Reserve, near Colesberg in the Karoo, and the Woodland Hills Wildlife Estate in Bloemfontein are all ideal for studying crucial aspects such as “faster than walking” speeds and gaits to measure key parameters (such as stride length, step frequency and stride duration). These studies are important to understand how giraffe form and function are adapted to their full range of locomotor behaviours. It also helps to comprehend the limits on athletic capacity in giraffes and how these compare to other animals.

Drones open up unique opportunities for studying giraffes

The increasing availability of unmanned aerial vehicles (UAVs)/drones opens up unique opportunities for studying locomotion in animals like giraffes. Cameras mounted onto remotely controlled UAVs are a straightforward way to obtain high-quality video footage of giraffes while they run at different speeds.

“Using two UAVs, we have collected high definition slow motion video footage of galloping giraffes from three locations in the Free State. We have also collected detailed information about the terrain that the giraffes walked and ran across. From this we have created 3D maps of the ground. These maps will be used to examine the preferred terrain types for giraffes, and to see how different terrains affect their locomotion and energy use,” said Dr Deacon.

“The raw data (videos) will be digitised to obtain the stride parameters and limb angles of the animals. Later this will be combined with anatomical data and an estimation of limb forces to estimate the power output of the limbs and how that changes between different terrains,” said Dr Basu.

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