Recent Advances in Diagnosis and Management of Female Genital Tuberculosis

Abstract

Female genital tuberculosis (FGTB) is an important cause of significant morbidity and infertility. Gold-standard diagnosis by demonstration of acid fast bacilli on microscopy or culture or detection of epithelioid granuloma on histopathology of endometrial or peritoneal biopsy is positive in only small percentage of cases due to its paucibacillary nature. Use of gene Xpert on endometrial or peritoneal biopsy has improved sensitivity of diagnosis. Composite reference standard (CRS) is a significant landmark in its diagnosis in which combination of factors like AFB on microscopy or culture, positive gene Xpert, epithelioid granuloma on endometrial or peritoneal biopsy, demonstration of definite or probable findings of FGTB on laparoscopy or hysteroscopy. There have been many advances and changes in management of FGTB recently. The program is now called National Tuberculosis Elimination Program (NTEP), and categorization of TB has been stopped. Now, patients are divided into drug-sensitive FGTB for which rifampicin (R), isoniazid (H), pyrazinamide (Z) and ethambutol (E) are given orally daily for 2 months followed by three drugs (rifampicin, isoniazid and ethambutol (RHE) orally daily for next 4 months. Multi-drug-resistant FGTB is treated with shorter MDR TB regimen of 9–11 months or longer MDR TB regimen of 18–20 months with reserved drugs. In vitro fertilization and embryo transfer have good results for blocked tubes and receptive endometrium, while surrogacy or adoption is advised for severe grades of Asherman’s syndrome.

Tuberculosis in the Female Genital Tract

“…FGTB can result in irreversible harm to the genital tract of women at progressive levels. Therefore, for the sake of prevention, early detection and management at the subclinical level is the only way to stop enduring harm and sequelae of the genital area of the woman with a thriving result of pregnancy [ 7 ]. Patients who already suffer from HIV infection or any other form of acquired or innate immuno-compromised states are more at risk.…”

Tuberculosis: An Overview of the Immunogenic Response, Disease Progression, and Medicinal Chemistry Efforts in the Last Decade toward the Development of Potential Drugs for Extensively Drug-Resistant Tuberculosis Strains

“…81 However, recent studies have shown that this four-drug treatment makes Mtb more susceptible to become drug-resistant in immunocompromised individuals. 86 Second-line drugs, such as fluoroquinolones (ciprofloxacin (7), gemifloxacin (8), and moxifloxacin (9)), 87 kanamycin (10), capreomycin (11), and viomycin (12) are a part of successful therapeutic regimens for treating MDR-TB. However, inadequate, incomplete, or poor treatment has led to XDR-TB, wherein the bacterial strain is not only resistant to isoniazid and rifampicin, as in the case of MDR-TB, but also to fluoroquinolones and at least to one of the three injectable second-line drugs (Figure 6b).…”

“…Moreover, it was structurally interesting and was a starting point good enough for the design of new potential more potent anti-TB drugs. In fact, this lead compound, having a nonbasic heteroaromatic moiety at the C-7 position, differs from clinically useful fluoroquinolones ciprofloxacin (7) and levofloxacin (50) (Figure 29). This is characterized by the presence of pyrrolidine-/piperazine-based substituents that have been widely explored to improve pharmacodynamic and pharmacokinetic profiles of fluoroquinolones.…”

“…The fluoro substituent at the C-6 position was retained, as desfluoro derivatives of pirfloxacin were inactive against mycobacteria. 267 Out of 21 newly synthesized molecules, quinolones 53o and 53n were as potent as ciprofloxacin (7) and levofloxacin (40) for the Mtb H37Rv strain and maintained the same activity during the five weeks of the assay (same MIC value of 0.25 μg/ mL, Table 19), while most of the other compounds proved to be less favorable for antitubercular activity. The two most active fluoroquinolones 53o and 53n retained their anti-TB activity when tested against one fluoroquinolone-sensitive and nine fluoroquinolone-resistant clinical isolates of Mtb (Table 20) bearing different point mutations in QRDRs of gyrA and gyrB genes.…”

“…MIC (μg/mL) of Compounds 53a−u and Positive Controls Ciprofloxacin(7) and Levofloxacin(50) against Mtb H37Rv…”