Clinical symptoms of active tuberculosis (TB) can range from a simple cough to more severe reactions, such as irreversible lung damage and, eventually, death, depending on disease progression. In addition to its clinical presentation, TB has been associated with several other disease-induced systemic complications, such as hyponatremia and glucose intolerance. Here, we provide an overview of the known, although ill-described, underlying biochemical mechanisms responsible for the clinical and systemic presentations associated with this disease and discuss novel hypotheses recently generated by various omics technologies.

The intricate relationship between HIV and TB, particularly in South Africa which grapples with an alarming prevalence of both diseases, presents a multifaceted challenge influenced by historical, social, and biological factors. This review explores the co-dependent nature of these diseases and the challenges to effective control strategies. The ramifications of Apartheid significantly shaped these pandemics, with TB thriving in impoverished conditions marked by overcrowding and limited health care access. Co-infection intensifies health challenges, further complicating treatment and management. Despite commendable efforts, achieving the ambitious “End TB” and “End HIV” goals set by the World Health Organization (WHO) for 2030 remains intricate due to socio-economic disparities, health care constraints, and political dynamics. The recent emergence of the COVID-19 pandemic introduced additional complexities, disrupting diagnostic and treatment services. Nevertheless, South Africa’s resilience is evident through destigmatisation campaigns, innovative preventative interventions, and significant contributions to global research. The importance of prevalence studies cannot be overstated; accurate data collection and analysis remain pivotal for informed interventions and tracking progress towards WHO goals. Here, we elucidate the need for a unified and comprehensive national response, supported by international collaboration, to effectively address the enduring HIV and TB burden within South Africa. As the nation navigates intricate historical legacies, social factors, and evolving health challenges, a crucial question arises: Will South Africa ultimately meet the WHO’s elimination goals or at least reduce the number of HIV-related TB deaths? Recognising potential obstacles, it becomes imperative to strategise responses to enable effective syndemic management and advancement towards WHO’s objectives.

Numerous studies have contributed to our current understanding of the complex biology of pulmonary tuberculosis and subsequently provided solutions to its control or eradication. Metabolomics, a newcomer to the Omics research domain, has significantly contributed to this understanding by identifying biomarkers originating from the disease-associated metabolome adaptations of both the microbe and host. These biomarkers have shed light on previously unknown disease mechanisms, many of which have been implemented toward the development of improved diagnostic strategies. In this review, we will discuss the role that metabolomics has played in tuberculosis research to date, with a specific focus on new biomarker identification, and how these have contributed to improved disease characterization and diagnostics, and their potential clinical applications.

Background: The synergy between the human immunodeficiency virus (HIV) and Mycobacterium tuberculosis during co-infection of a host is well known. While this synergy is known to be driven by immunological deterioration, the metabolic mechanisms that contribute to the associated disease burden experienced during HIV/tuberculosis (TB) co-infection remain poorly understood. Furthermore, while anti-HIV treatments suppress viral replication, these therapeutics give rise to host metabolic disruption and adaptations beyond that induced by only infection or disease. Methods: In this study, the serum metabolic profiles of healthy controls, untreated HIV-negative TB-positive patients, untreated HIV/TB co-infected patients, and HIV/TB co-infected patients on antiretroviral therapy (ART), were measured using two-dimensional gas chromatography time-of-flight mass spectrometry. Since no global metabolic profile for HIV/TB co-infection and the effect of ART has been published to date, this pilot study aimed to elucidate the general areas of metabolism affected during such conditions. Results: HIV/TB co-infection induced significant changes to the host’s lipid and protein metabolism, with additional microbial product translocation from the gut to the blood. The results suggest that HIV augments TB synergistically, at least in part, contributing to increased inflammation, oxidative stress, ART-induced mitochondrial damage, and its detrimental effects on gut health, which in turn, affects energy availability. ART reverses these trends to some extent in HIV/TB co-infected patients but not to that of healthy controls. Conclusion: This study generated several new hypotheses that could direct future metabolic studies, which could be combined with other research techniques or methodologies to further elucidate the underlying mechanisms of these changes.