Effect of DOTS Treatment on Vitamin D Levels in Pulmonary Tuberculosis

Abstract

INTRODUCTIONPTB is associated with weight loss, nutritional deficiency and impaired metabolism [6]. In the prebiotic era, sun exposure, TB sanatorium and cod liver oil were commonly used to treat patients infected with TB. All these incidentally are good sources of Vit D [2,7]. DOTS is the current treatment modality for TB which comprises of administration of anti-tubercular drugs in two phases, intensive phase and continuous phase [8]. With the advent of effective antituberculosis drugs, enthusiasm for treating TB with the earlier Vit D rich modalities subsided [9]. Impaired metabolism in PTB may possibly worsen the effects of VDD [6]. In TB, liver functions may be hampered by diffuse hepatic involvement, granulomatous hepatitis or local abscess formation [10].Previous reports on the interaction between Vit D and anti-tubercular drugs have shown that, rifampicin causes an accelerated loss of Vit D due to increased clearance as it acts as an agonist to pregnane X receptor and inducing the activity of CYP3A4 and limiting the formation of active one alpha 25(OH)2D3 [11]. CYP3A4, a hepatic cytochrome P450 enzyme is involved in drug metabolism, and catabolism of Vit D via a similar pathway as CYP24A1 (an enzyme catalysing the hydroxylation steps of Vit D2 and Vit D3) [12]. Isoniazid causes impairment of 25-hydroxylation leading to impaired Vit D action [13,14], although pyrazinamide, isoniazid and rifampicin have all been associated with hepatotoxicity and the risk is enhanced when these drugs are used in combination. Studies have reported 1-31% of TB patients experience drug related hepatotoxicity following TB treatment [15]. However, isoniazid and ethambutol have been associated with acute kidney injury, rifampin is the most common as reported by most studies [16,17]. Immune responses to TB are influenced by a variety of factors, including younger age [18], diabetes mellitus, tobacco smoking, alcohol, immunosuppressive drugs [19], HIV status, and concurrent infections. Cachexia has been linked to poor prognosis and is a major risk factor for mortality [20]. All these factors are also associated with VDD [21]. The underlying mechanism of how Vit D metabolisms could be linked to the pathophysiology of PTB is complex and not fully understood. This research was carried out to study the changes in Vit D levels in active PTB, the effect of DOTS on Vit D status and alterations in hepatic and renal profiles possibly contributing to the effects.

Immunologic Effects of Vitamin D on Human Health and Disease

“…In the presence of overt granulomatous inflammation, the increase in circulating 1,25(OH) 2 D produced by activated macrophages and monocytes results in up-regulation of the expression of CYP24A1 encoding the enzyme 25-hydroxyvitamin D-24-hydroxylase, which, in turn, converts 25(OH)D and 1,25(OH) 2 D into a water-soluble inactive carboxylic acids [ 2 , 6 , 148 ]. Moreover, serum 25(OH)D levels can be affected by anti-tuberculosis and concurrent medications such as antiretroviral drugs which are commonly used for treatment of comorbid HIV infection [ 2 , 149 ]. On the other hand, the association could be explained by the insufficient amount of 25(OH)D substrate required for the conversion into 1,25(OH) 2 D to stimulate granulomatous immune response against the invading organisms.…”

Vitamin D and tuberculosis: where next?

“…Apart from their bactericidal or bacteriostatic actions, standard antibiotics can also modulate host immune responses such as phagocytosis, chemotaxis, antigen presentation, cytokine secretions and autophagy . Furthermore, intensive‐phase treatment with rifampicin and isoniazid has been shown to reduce baseline vitamin D levels in the majority of treated TB patients, which suggests that standard treatment alone may promote vitamin D deficiency or worsen an already low vitamin D status .…”

Vitamin D Deficiency is Less Prevalent Among Children with Common Medical Illnesses than Apparently Healthy Children in Sub-Saharan Africa: A Systematic Review and Meta-Analysis

“…individual studies conducted elsewhere which shows vitamin D deficiency more prevalent among people with some type illnesses and health conditions [28,29]. In the current study the lesser prevalence of vitamin D among sick children than healthy children might be due to the fact that, most of the studies included for the sick children were conducted among some studies among HIV patients show that ART treatment drugs particularly, use of ritonavir or tenofovir, was associated with higher levels of 25OHD [35] and this might also be contributed for higher vitamin D among the sick groups.…”