Tuberculosis Research @ NMIMR:

From Field Through Basic Research to TB Control

Tuberculosis (TB) is a disease of antiquity and eradication of it has been man’s dream throughout history. According to the World Health Organization (WHO) estimates, about a quarter of the world’s population are latently infected with the causative agent, thus, creating a pool of future active cases. Globally, in 2020 alone, an estimated 9.9 million new TB cases occurred, out of which 1.5 million died of TB making TB the number two infectious disease killer by a single infectious agent only second to COVID-19. To reduce this high global TB burden, the WHO put in a strategy known as the “End TB Strategy” in 2014 with set targets to reduce the absolute number of TB deaths and TB incidence by 90 and 80% respectively by 2030 and 95 and 90% respectively by 2035. The End TB strategy outlines three pillars including (1) an integrated, patient-centered care and prevention, (2) bold policies and supportive systems, and (3) intensified research and innovation. Our research activities, together with the national TB control program (NTP) is geared towards addressing the set pillars of the End TB strategy through activities that commence from the field pass through the lab and culminate in TB control. Our support to the NTP ranges from diagnosis and basic epidemiological research to public and community engagement activities.

In 2020, TB incidence and mortality rate in Ghana was estimated to be respectively 143 and 49 per 100,000 population, indicating that a third of our estimated TB cases die from the infection. It is worrying to note that only a third of the estimated incidence are notified at the health centers. To curb the local TB burden while influencing the global burden, several TB research activities are conducted in the bacteriology department including basic research to understand the biology of the causative pathogen, Paediatric related TB research to improve TB diagnosis among children, comorbidity and gut microbiome studies to understand the role of co-infection with other communicable and non-communicable diseases, one health research to track and prevent zoonotic transmission and trainings, monitoring and national diagnostic support towards detecting and tracking multi drug resistant TB strains.

Basic Tuberculosis Research
Before the 19th century, very little was known about the causative pathogen and disease mechanisms. Now we know that tuberculosis in mammals is mainly caused by at least 9 genetically related mycobacterial species comprising Mycobacterium tuberculosis sensu stricto (Mtb), M. africanum (Maf), M. bovis, M. mungi, M. microti, M. caprae, M. pinnipedii, M. suricattae, and M. orygis together referred to as the M. tuberculosis complex (MTBC). Previously thought to be a monomorphic bacterium, current application of next generation sequencing tools has revealed substantial genomic differences within members of the complex. In our lab, our basic TB research aims to understand the biology and transmission of the causative pathogen as well as gain insight into understanding host-pathogen interactions using various approaches comprising basic molecular epidemiology, genomic epidemiology, comparative genomics, phenotypic and genotypic analysis, and immunology.
Paediatric TB Research
Although the highest global burden of TB is in adults, in 2020, children accounted for 11%. In Ghana, 5% of TB incidence is due to childhood TB. Many young children cannot produce the sample (sputum) required for the existing test for pulmonary tuberculosis (TB). Consequently, diagnosis is often based on clinical signs, symptoms, and history of TB contact. This situation has led to some children dying from undiagnosed TB or being treated wrongly for TB. Of the estimated 230,000 children who died of TB in 2018, 80% were less than 5 years and 96% of deaths occurred before treatment started. It has also been established that when treatment is started early due to early diagnosis, success rate is over 90%.  Our study aims to determine the usefulness of blood/urine- based tests and cytokine biomarkers in improving the diagnosis of TB in children and the risk factors for childhood TB in Ghana.
Tuberculosis Comorbidity
Tuberculosis coinfection with other communicable and non-communicable diseases as well as the diverse gut microbiome of individuals may influence TB treatment outcome. The department, through its research activities, has devoted several resources to understand the role of comorbidity and gut microbiome in TB disease. Diabetes mellitus (DM) is increasingly becoming a worldwide chronic health condition, which can be attributed to increases in obesity, changing patterns of diet and physical activity as well as ageing. DM has been associated with reduced T cell response and neutrophil functional activity. Reports of many studies in different parts of the world indicated a higher DM prevalence among newly diagnosed TB cases compared to the general population. However, unlike HIV/AIDS, the relationship between TB and DM has not been giving much attention, especially in low-income countries where 75% of diabetic patients live and are also battling with TB.
Gut Microbiome Studies

TB depletes the gut microbiome of beneficial bacteria and in the cases of comorbidity depletion is more severe which could negatively impact treatment outcome. Our preliminary findings indicate that, the gut microbiome in TB patients living with diabetes and/or HIV is depleted of beneficial bacteria such as Bifidobacterium, Faecalibacteriun and Clostridium with enrichment in inflammation related bacteria

One Health Research on Tuberculosis
The Mycobacterium tuberculosis complex (MTBC) consists of two main groups of organisms, the human adapted MTBC (hMTBC) and the animal adapted MTBC (aMTBC). Although each category of organisms are adapted to infecting their unique hosts, as the names suggests, occasionally, there is cross specie infection leading to zoonosis. One of the organisms that is widely involved in zoonosis is the Mycobacterium bovis which causes bovine tuberculosis (BTB). BTB is a disease of global public and animal health significance. The disease is endemic in major livestock producing countries in sub-Saharan Africa. Little or no attention is given to the disease and its impact on livestock and humans. Within the past decade we have been involved in a number of projects aimed at identifying and characterizing aMTBC and tracking zoonotic transmission by adopting a One Health concept.
National Diagnosis Support, Trainings and Monitoring

Tuberculosis is a disease of antiquity but still a global health challenge. It had always been the leading cause of death by a single infectious disease till the emergence of COVID-19. The emergence and rapid rise in the number of drug-resistant TB cases in Ghana is a huge threat to the Ghanaian health system, this has led the NTP in collaboration with partners such as NMIMR to embark on this active case search in Out-patient departments in hospitals to trace, test and treat TB in its early stages to reduce morbidity and mortality. Since TB treatment is individualized, we follow-up on patients throughout all 6 to 24 months in the cases of drug-resistant TB, conducting various tests to determine whether or not drug therapy is successful or fails.