Abstract
Extra-pulmonary tuberculosis (EPTB) is recognized mainly as a secondary manifestation of a primary tuberculosis (TB) infection in the lungs contributing to a high incidence of morbidity and mortality. The TB bacilli upon reactivation maneuver from the primary site disseminating to other organs. Diagnosis and treatment of EPTB remains challenging due to the abstruse positioning of the infected organs and the associated invasiveness of sample acquisition as well as misdiagnosis, associated comorbidities, and the inadequacy of biomarkers. Female genital tuberculosis (FGTB) represents the most perilous form of EPTB leading to poor uterine receptivity (UR), recurrent implantation failure and infertility in females. Although the number of TB cases is reducing, FGTB cases are not getting enough attention because of a lack of clinical awareness, nonspecific symptoms, and inappropriate diagnostic measures. This review provides an overview for EPTB, particularly FGTB diagnostics and treatment challenges. We emphasize the need for new therapeutics and highlight the need for the exaction of biomarkers as a point of care diagnostic. Nuclear receptors have reported role in maintaining UR, immune modulation, and TB modulation; therefore, we postulate their role as a therapeutic drug target and biomarker that should be explored in FGTB.
Highlights
Mycobacterium tuberculosis (M. tuberculosis) is an etiological agent that causes tuberculosis (TB), which is a health issue of global importance
This review provides an overview for extrapulmonary tuberculosis (EPTB), female genital TB (FGTB) diagnostics and treatment challenges
The most prevalent site of TB infection is the lungs; this is called pulmonary TB (PTB), where the bacilli are phagocytosed in alveolar macrophages and are contagious via Abbreviations: EPTB, Extrapulmonary Tuberculosis; PTB, Pulmonary Tuberculosis; TB, Tuberculosis; FGTB, Female Genital Tuberculosis; recurrent implantation failure (RIF), Recurrent Implantation Failure; uterine receptivity (UR), Uterine Receptivity; endometrium regeneration (ER), Endometrium regeneration; cytokine modulation (CM), Cytokine modulation; leukemia inhibitory factor (LIF), Leukemia inhibitory factor; vascular endothelial growth factor (VEGF), Vascular endothelial growth factor; NR, Nuclear Receptors; TR4, Testicular receptor; PPAR, Peroxisome Proliferator Activated Receptor; pregnane X receptor (PXR), Pregnane X Receptor; vitamin D receptor (VDR), Vitamin D Receptor; liver X receptor (LXR), Liver X Receptor; progesterone receptor (PR), Progesterone receptor; liver receptor homolog 1 (LRH1), Liver receptor homolog 1; nuclear receptor related (Nurr), Nuclear receptor related; androgen receptor (AR), Androgen receptor; COUP-TF, Chicken Ovalbumin Upstream Promoter; SF-1, Steroidogenic Factor; farnesoid X receptor (FXR), Farnesoid X Receptor; IL, Interleukin
Summary
Mycobacterium tuberculosis (M. tuberculosis) is an etiological agent that causes tuberculosis (TB), which is a health issue of global importance. TB bacilli can disseminate to other organs and causes extrapulmonary tuberculosis (EPTB). The genital organs are an important site for dissemination. EPTB is mainly considered to be a secondary manifestation of the primary infection, which is rarely contagious; extrapulmonary involvement can occur with or without PTB. The World Health Organization (WHO) reported 7 million TB cases in 2018 of which 15% were EPTB [2]. Approximately, 10%–50% of EPTB cases are reported to have pulmonary manifestation [3]. FGTB, which represents the most perilous form of EPTB, is steadily rising as one of the major causes of infertility in females. Primary infection of TB in the genital tract of females, albeit rare, may occur if the partner has active genitourinary TB. It is vital that research into EPTB and especially FGTB is increased as it is critical to enhance our knowledge of this disease in order to effectively combat it
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