Criteria for Monitoring the Treatment Efficacy of Female Genital Tuberculosis

Tuberculosis (TB) remains a major public health problem globally. Female genital tuberculosis (FGT) occurs mostly secondary to pulmonary tuberculosis, commonly by the haematogenous route. The main difficulties in the monitoring of treatment efficacy are connected with the use of the same technologies both in the diagnosis and cure estimation of FGT. Articles in tuberculosis journals rarely featured by equations. The aim of the present study was to elaborate new analytical approaches, in form of equation concerning FGT treatment efficacy identification. The general conclusion was created towards the RCSR (red cells sedimentation rate), PCR (polymerase chain reaction) and tuberculin skin-test, ultrasound and radial examinations: they are not reliable tools since both false–negative or false–positive cases were observed . Explanation of the mismatch of the most of identified alterations by means of ultrasound and radial examinations (CT and MRI) with the clinical status of women is explained by the prolonged maintenance of alterations caused by disease, up till several years after clinical recovery. Newly elaborated test based on 1H–NMR (T1, T2), relaxation times measurement in vitro being combined with the regression analysis models have a potential to assess the treatment efficacy of female genital tuberculosis in 70% of cases.


Introduction
Tuberculosis (TB) is an increasing public health concern worldwide with about six million new cases a year. It is one of the most important causes of infectious morbidity and mortality. On a global scale, TB has a devastating impact on developing nations with 13 countries accounting for nearly 75% of all cases [1]. World health organization (WHO) classifies FGT as category III (extrapulmonary, sputum smear-negative, not seriously ill (SSNFGT)) [2]. FGT affects about 12% of patients with pulmonary tuberculosis [3] and represents 15-20% of extrapulmonary tuberculosis [4]. FGT occurs mostly secondary to pulmonary tuberculosis, commonly by the haematogenous route in a manner similar to spread to other extra-pulmonary sites like urinary tract, bones and joints etc.
Remarkably, despite of a wealth of information, clinical physicians and TB biologists possess virtually no comprehensive theoretical model which could serve as a framework for understanding, organizing and applying these data. Continuing search is needed for finding simpler and practicable methods for making diagnosis in respect of FGT easier and the use of therapeutic test should be avoided. Diagnosis of FGT is made by meticulous patients history study, thorough clinical examination and proper use of investigations, particularly endometrial aspirate for AFB (Acid Fast Bacilli :tuberculosis test: organisms (including mycobacteria) that resist decolorization with acid alcohol due to the lipid-rich mycolic acids in the cell wall thereby retaining the primary stain) culture, PCR and histopathology aided by endoscopy It may be mentioned that research is considerably hampered due to a non-availability of clear criteria for monitoring the treatment efficacy, unlike in pulmonary TB [5]. Therefore, more research is needed, so that delivery of therapy can become more certain and therapeutic effects get better defined in terms of the normalization of the pathologic process and the desirable reproductive function [6]. Therefore, all the available diagnostic techniques should be combined judiciously and correlated with the clinical profile prior to instituting the treatment of tuberculosis [7]. The main difficulties in the monitoring of treatment efficacy are connected with the use of the same technologies both in the diagnosis and cure estimation of TB. Articles in tuberculosis journals rarely featured by equations.
Apparently, as a reason of it could be the fact that mathematical

Material and Methods
Objects: Cohort

Biological Specimens for Laboratory Analyses
Blood for the 1 H-NMR (T 1 , T 2 ) relaxation times measurements and polymerase chain reaction was yielded from the venum cubitalis by means of syringe and needle, oxaloacetate was used as a stabilizer, volume 5 mL; blood plasma was obtained by spinning of blood at 5000 rounds/per minute during 20 minutes. Vaginal lavage: vagina and vaginal part of the cervix uteri was dried by gauze plug, 5,0 mL of 0,86% NaCl sterilized solution was poured to the vagina, exposed there during 20 minutes, lavage was sucked by means of the sterilized syringe and put to the glass tube.

Laboratory Techniques
PCR was performed on the equipment of "DNA-technology" (Russia) using reagents of "Flash" (Russia). Tuberculin-skin-test was performed with the purified, liquid tuberculosis allergen, manufactured by "Biolek" (Ukraine), standard dilutions were used for the intradermal application. Tuberculosis allergen was injected to the arm, allergen's IV (10 Tuberculosis units) and VI (0,01 Tuberculosis unit) dilutions were used. Tuberculin-test reaction was estimated by passing 72 hours. papule ≥5 mm was considered as a positive result. RCSR was revealed [7].

Statistical Calculations
Statistical calculations have been performed by means of Informative value of the regression equations has been estimated according to R 2 (determination coefficient) meaning, statistical significance was assessed according to Fisher's F-factor.

All the scientific researches fit to the rules of the Ethical Control
Commission, sanitarian and regimes against infection.

Result and Discussion
Although FGT can occur in any age group, the majority of patients are usually belonging to the reproductive group of age, 75% are in the 20-45 years age bracket, postmenopausal women account for 11% of cases of FGT [6]. In our investigations they amounted 84,2%, and 12,3% of cases respectively (Table 1).  (Table 1) & [8,9]. Systemic constitutional symptoms of the weight loss, feeling unwell and night sweats may be present. Attendant disease is very frequent, 96,5% (Table 1). In the postmenopausal women, FGT is combined with postmenopausal bleeding, persistent leucorrhoea. Note: Number (%) of cases.
During the entire course of cure patient with TB is undergoing to more than 80 types of heamatological, cytological, biochemical,  (Table 2).

Radial Studies In Vivo
USG. All the recovered patients were featured by the pathological changes of anatomical structures, some of these changes were revealed in 100% (Table 4). HSG. HSG is performed frequently as an investigation for infertility [7], what is a common complication of genital TB. It should not be performed when TB is diagnosed by other means, as it may result in dissemination and flare-up of disease. Tubal occlusion is the most frequent HSG finding in genital tuberculosis (Table 4).  Further investigation has been focused on the radio spectroscopy parameters of 1 H-NMR relaxation T 1 , T 2 times measurements in vitro.

Radial Studies In Vitro
NMR. 1 H-NMR (T 1 , T 2 ) relaxation times reflects the change of metallic ions, diamagnetics, high molecular weight compounds and low molecular weight ligands contents. Additionally T 1 , T 2 values are stipulated by the capacity of molecules, which are the constituents of tissues, to induce formation of the "hydration water", the water shell, and by the thickness of shell, which in turn is stipulated by the conformation and the composition of the biochemical structures exposed to the water phase. The mostly probable molecular substrate of the nature of the water 1 H-NMR relaxation times (T 1 , T 2 ), gained in blood serum, in some of diseases, is seemed to be a fraction of the low molecular weight compounds with the mass approximately5000 Da. We have failed to yield statistical significant differences between I, II, III subgroups of women in NMR investigations, while deviations from the normal value ranges up to 60% have been observed ( Table 5). Identification of FGT treatment efficacy according to direct T 1 , T 2 measurements, based on the descriptive statistics, is not available.

Regressions Analyses
Preliminary all above investigated parameters have been considered in terms of the descriptive statistics (Tables 3-6).