An Introduction: Stool4TB PhD Students

The Stool4TB project has recently selected PhD students to conduct research embedded within the project. The PhD students have the opportunity to work alongside experts in tuberculosis in three African countries. Edson Tereso Mambuque, from Mozambique, George William Kasule, from Uganda, and Busizwe Sibandze from Eswatini, join the Stool4TB project and pursue their own interests surrounding TB during their PhD journeys. Edson, George, and Busizwe share with us their interest in TB and their ambition for a PhD.

Could you briefly introduce yourself?  

My name is Edson Tereso Mambuque and I am a Laboratory Technician, deeply interested in biomedical research since I started as a trainee in biology back in 2015. I am currently coordinating the TB laboratory and different studies on TB Clinical trials, TB epidemiology, and TB diagnostics at Manhiça Health Research Center [in Mozambique].

I am George William Kasule, a biomedical laboratory scientist with about 10 years of working experience in the Uganda National TB Reference Laboratory (NTRL) in diverse TB diagnostics. I obtained both bachelor’s and master’s degrees at Makerere University, Uganda. I have participated in research on Mycobacterium tuberculosis with several publications. I have a passion for operational and translational science research, especially in HIV/TB co-infection.

My name is Doctor Busizwe Sibandze. I am a Medical Laboratory Scientist with Masters’ and Honors degrees in Medical Microbiology both from the University of Pretoria. I did my first degree at the University of Stellenbosch where I majored in Human Physiology and Microbiology. At present, I am leading the implementation of sequencing technology project which is a collaborative initiative of the Ministry of Health of the Government of Eswatini, Research Center Borstel Leibniz Lung Center, Ospedale San Raffaele, Baylor College of Medicine, and the Baylor College of Medicine Children’s Foundation of Eswatini. This project is part of the SeqMDRTB_NET: Global Health Protection Programme which funded by the government of Germany. This project aims to establish sequencing technologies as diagnostic tool for the rapid prediction of drug resistance in Eswatini. Previous notable projects include; TB Drug Resistance Survey, TB Prevalence Survey and Population-based HIV Impact Assessment Survey (SHIMS3, 2020). Given the extensive experience I have gained in the different national surveys, I have developed interest in infectious diseases especially in TB and HIV. My MSc dissertation aimed to describe the occurrence of heterogeneity and heteroresistance in patient with both pulmonary and extra-pulmonary TB.

 

What is your PhD is going to entail?  

Edson Tereso Mambuque: My PhD research in the Stool4TB project focuses on the microbiome and molecular characterization of variations in sputum and stool for TB diagnosis among children and adults.

George William Kasule:  My PhD research is nested in the Stool4TB project; ‘Evaluation of non-sputum-based biomarkers for TB diagnosis among children and People Living with HIV’. TB Biomarkers in non-sputum specimens; stool, urine, and breath condensates have shown a great potential of filling the limitations of sputum TB diagnosis where little is documented among children and PLHIV that are usually difficult to diagnose population

Busizwe Sibandze: For my PhD, I will study evolution of I491F mutation which is of molecular epidemiology importance in Eswatini by comparing strains from 2009/2010 and 2017/2018 drug resistance surveys. Furthermore, I will investigate the emergence of other MDR strains due low level mutations including bedaquiline/ clofazimine. The aim is to compare the physiological state of MDR strains cause by I491F mutation and other low level mutations (at baseline and during treatment with bedaquiline/ clofazimine) using a biorepository from the Stool4TB Samples. Samples will include; all Baseline samples of patients enrolled into the study, samples of patients failing to culture convert at 4 months, samples of patients with culture reversion. Lastly, I will investigate the complexity of infections and detection of both minority and major variants within a single host from these samples.

 

What made you interested in this PhD position?

Edson Tereso Mambuque: My first contact with the molecular biology of TB was 5 years ago when I successfully performed the first local molecular epidemiology study of M. tuberculosis from the remnants of samples in Genexpert cartridges entitled "Direct genotyping of Mycobacterium tuberculosis from GeneXpert® MTB/RIF remnants"; whose article has already been published in the international journal Tuberculosis.

Recently, I concluded my master’s degree in Medical Microbiology with work entitled "Evaluation of cutting-edge diagnostic and treatment monitoring tools in a cohort of TB patients during the first month of treatment" where it was possible to evaluate phenotypic and genotypic tools to characterize the susceptibility profile of MTBC isolates during treatment. Additional analysis is still ongoing, and some issues related to genetic profile could better be understood if genomic tools were applied. Nevertheless, due to time and resource limitations we were not able to continue the analysis.

During these years, I acquired a wide spectrum of knowledge important for research in general and in the field of TB in particular, however, a PhD in TB genomics will fill some of the gaps identified during my master’s work to consolidate and strengthen leadership skills and to assess and design genomic tools needed to continue with my research career.

George William Kasule:  TB is the leading cause of death among HIV patients, and it is more challenging to diagnose TB among children and PLHIV. These statistics can be improved through early, accurate, and reliable diagnostics. This PhD project aims for a better TB diagnostic technique in children and PLHIV is in line with my research interests in infectious diseases of TB, HIV, and related diseases.

Busizwe Sibandze: Personally, I have always had a desire to grow my skills and become an effective Microbiologist in Eswatini but one had to find balance in growing my career as a scientist and pursuing my academic endeavors. So when the opportunity to pursue my PhD through the Stool4TB project using data from Eswatini presented itself will knew this was my moment. Since the Stool4TB Project seeks to identify newer tools to address TB in a population of patients that may not be able to produce sputum, I saw this as an opportunity to maintain my position in the country where I’m currently implementing sequencing technology for the fight against drug resistance in TB.

 

What do you hope to gain from working on Stool4TB?

Edson Tereso Mambuque: From the biorepository of Stool4TB studies we may be able to answer questions related to microbiome signatures that may be used to diagnose tuberculosis diagnosis and indicate progression to disease or clinical outcomes and could be used as recommendations to identification and validation assays applied in high-tuberculosis burden and HIV- prevalent settings.

George William Kasule: The knowledge and skills I will acquire from this PhD program as well as from working with a team of people with diverse skills and expertise in the fields of biomedical sciences such as immunology, molecular biology, etc., are fundamental for operational and translational science. This PhD will be my basis for further research in developing better TB diagnosis tools in children and PLHIV that eventually be translated into policy changes locally and globally.

Busizwe Sibandze: I hope to grow my skill as an and learn how to perform Minimal inhibitory concentrations MICs for drug susceptibility testing (including the understanding of the epidemiological cut off values), RNA sequencing and whole genome sequencing. With regards to the dry laboratory, I hope to learn the follows; how to perform Phylogenetic analysis, whole-genome single-nucleotide polymorphism (SNP) analysis, Structural analysis in proteins using visual and computational analyses and bioinformatics analysis. Lastly, I hope to also gain skill as far as entrepreneurship, grantsmanship writing, become an independent Researcher.

 

What inspired you to work in the field of TB?  

Edson Tereso Mambuque: As a biomedical researcher, I believe that the results generated in our research centre may help to fulfil the estimation gaps or answer the underestimated numbers due to the lack of laboratory facilities in Southern African countries. Additionally, Mozambique is still included in the list of 30 TB/HIV high burden countries for many years, ranking third and sixth in TB incidence and mortality, respectively. Laboratories have a critical role in the WHO’s End TB Strategy which calls for the early diagnosis of TB and universal drug-susceptibility testing (DST) emphasizes in order to meet the targets.

Additionally, few data on the microbiome are available in Southern African countries from those patient populations that are epidemiologically important, at elevated risk of poor outcomes, and have compromised capacity to control resident microbial communities.

George William Kasule: TB research in diagnostics has transformed in the last few decades at a tremendous speed that led to many policy changes worldwide; from the use of TB microscopy to rapid molecular techniques with better performance of sensitivity. Having worked in TB diagnostics and lab strengthening for about 10 years exposed me to the first-hand experience of this transformation and this has always inspired me to continue in this field because through more research, better TB diagnostic tools can be discovered/developed.

Busizwe Sibandze: Tuberculosis is the far most global disease that soared over decades devastating the world. Meeting the world’s challenges through science is my source of inspiration. A healthy society is a wealthy society therefore, as scientists we need to work around the clock to ensure we respond to pandemics appropriately and timeously.

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