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11 December 2019 | Story Leonie Bolleurs
Aids read more

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

Inaugural lecture: Prof Robert Bragg, Dept. of Microbial, Biochemical and Food Biotechnology
2006-05-17



Attending the inaugural lecture were in front from the left Prof Robert Bragg (lecturer at the Department of Microbial, Biochemical and Food Biotechnology) and Frederick Fourie (Rector and Vice-Chancellor).  At the back from the left were Prof James du Preez (Departmental Chairperson:  Department of Microbial, Biochemical and Food Biotechnology) and Prof Herman van Schalkwyk (Dean: Faculty of Natural and Agricultural Sciences). Photo: Stephen Collett
 

A summary of an inaugural lecture delivered by Prof Robert Bragg at the University of the Free State:

CONTROL OF INFECTIOUS AVIAN DISEASES – LESSONS FOR MAN?

Prof Robert R Bragg
Department of Microbial, Biochemical and Food Biotechnology
University of the Free State

“Many of the lessons learnt in disease control in poultry will have application on human medicine,” said Prof Robert Bragg, lecturer at the University of the Free State’s (UFS) Department of Microbial, Biochemical and Food Biotechnology during his inaugural lecture.

Prof Bragg said the development of vaccines remains the main stay of disease control in humans as well as in avian species.  Disease control can not rely on vaccination alone and other disease-control options must be examined.  

“With the increasing problems of antibiotic resistance, the use of disinfection and bio security are becoming more important,” he said.

“Avian influenza (AI) is an example of a disease which can spread from birds to humans.  Hopefully this virus will not develop human to human transmission,” said Prof Bragg.

According to Prof Bragg, South Africa is not on the migration route of water birds, which are the main transmitters of AI.  “This makes South Africa one of the countries less likely to get the disease,” he said.

If the AI virus does develop human to human transmission, it could make the 1918 flu pandemic pale into insignificance.  During the 1918 flu pandemic, the virus had a mortality rate of only 3%, yet more than 50 million people died.

Although the AI virus has not developed human-to-human transmission, all human cases have been related to direct contact with infected birds. The mortality rate in humans who have contracted this virus is 67%.

“Apart from the obvious fears for the human population, this virus is a very serious poultry pathogen and can cause 100% mortality in poultry populations.  Poultry meat and egg production is the staple protein source in most countries around the world. The virus is currently devastating the poultry industry world-wide,” said Prof Bragg.

Prof Bragg’s research activities on avian diseases started off with the investigation of diseases in poultry.  “The average life cycle of a broiler chicken is 42 days.  After this short time, they are slaughtered.  As a result of the short generation time in poultry, one can observe changes in microbial populations as a result of the use of vaccines, antibiotics and disinfectants,” said Prof Bragg.   

“Much of my research effort has been directed towards the control of infectious coryza in layers, which is caused by the bacterium Avibacterium paragallinarum.  This disease is a type of sinusitis in the layer chickens and can cause a drop in egg product of up to 40%,” said Prof Bragg.

The vaccines used around the world in an attempt to control this disease are all inactivated vaccines. One of the most important points is the selection of the correct strains of the bacterium to use in the vaccine.

Prof Bragg established that in South Africa, there are four different serovars of the bacterium and one of these, the serovar C-3 strain, was believed to be unique to Southern Africa. He also recently discovered this serovar for the first time in Israel, thus indicating that this serovar might have a wider distribution than originally believed.

Vaccines used in this country did not contain this serovar.  Prof Bragg established that the long term use of vaccines not containing the local South African strain resulted in a shift in the population distribution of the pathogen.

Prof Bragg’s research activities also include disease control in parrots and pigeons.   “One of the main research projects in my group is on the disease in parrots caused by the circovirus Beak and Feather Disease virus. This virus causes serious problems in the parrot breeding industry in this country. This virus is also threatening the highly endangered and endemic Cape Parrot,” said Prof Bragg.

Prof Bragg’s research group is currently working on the development of a DNA vaccine which will assist in the control of the disease, not only in the parrot breeding industry, but also to help the highly endangered Cape Parrot in its battle for survival.

“Not all of our research efforts are directed towards infectious coryza or the Beak and Feather Disease virus.  One of my Masters students is currently investigating the cell receptors involved in the binding of Newcastle Disease virus to cancerous cells and normal cells of humans. This work will also eventually lead to a possible treatment of cancer in humans and will assist with the development of a recombinant vaccine for Newcastle disease virus,” said Prof Bragg.

We are also currently investigating an “unknown” virus which causes disease problems in poultry in the Western Cape,” said Prof Bragg.
 
“Although disinfection has been extensively used in the poultry industry, it has only been done at the pre-placement stage. In other words, disinfectants are used before the birds are placed into the house. Once the birds are placed, all use of disinfectants stops,” said Prof Bragg.

“Disinfection and bio security can be seen as the ‘Cinderella’ of disease control in poultry.  This is also true for human medicine. One just has to look at the high numbers of people who die from hospital-acquired infections to realise that disinfection is not a concept which is really clear in human health care,” said Prof Bragg.

Much research has been done in the control of diseases through vaccination and through the use of antibiotics. “These pillars of disease control are, however, starting to crumble and more effort is needed on disinfection and bio security,” said Prof Bragg.

Prof Bragg has been working in close co-operation with a chemical manufacturing company in Stellenbosch to develop a unique disinfectant which his highly effective yet not toxic to the birds.

As a result of this unique product, he has developed the continual disinfection program for use in poultry. In this program the disinfectant is used throughout the production cycle of the birds. It is also used to ensure that there is excellent pre-placement disinfection.

“The program is extensively used for the control of infectious diseases in the parrot-breeding industry in South Africa and the product has been registered in 15 countries around the world with registration in the USA in the final process,” said Prof Bragg.

“Although the problem of plasmid mediated resistance to disinfectants is starting to rear its ugly head, this has allowed for the opening of a new research field which my group will hopefully exploit in the near future,” he said.

 

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