Immune disturbances in female genital tuberculosis and latent genital tuberculosis.

BACKGROUND: Female genital tuberculosis (FGTB), an important clinical sub-type of extra-pulmonary tuberculosis (EPTB) is responsible for about 10% cases of infertility in India. Both FGTB and latent genital tuberculosis (LGTB) can cause infertility through blockage of fallopian tubes and through altered uterine endometrial receptivity. AIMS: This review tries to elucidates the role of various immune factors in FGTB and LGTB. CONTENT: Various immune disturbances are observed in FGTB and LGTB like growth factors and cytokines which inhibit implantation and several inflammatory signaling pathways like mitogen activated protein kinase (MAPK), natural killer (NK) cells, nuclear factor kappa-B (NF-KB), tumor necrosis factor (TNF), and toll like receptors (TLR) signaling are dysregulated. These altered immune factors and pathways may be detected in the endometrial biopsies at the early stages of disease before permanent damage. Prompt and adequate treatment with the four anti-tubercular drugs (rifampicin [R], isoniazid [H], pyrazinamide [Z], and ethambutol [E]) can increase pregnancy rates in some of these women. Assisted reproduction especially in-vitro fertilization and embryo transfer may be required for some women. IMPLICATIONS: Inflammatory pathways identified from the gene profiling have enabled development of potential biomarkers for early diagnosis of FGTB. Immunomodulation and novel biotechniques like stem cell transplantation, nanoparticles and host directed therapies are being tried in selected patients of FGTB and LGTB with promising results.

Efficacy and Safety of COVID-19 Vaccines-An Update.

A few centuries ago, the first vaccine vial was formulated, and since then, they have resulted in an eminent reduction in infectious diseases associated morbidity and mortality. The discovery of the novel SARS-CoV-2 virus and the COVID-19 disease and its steady progression to a global pandemic with 603,711,760 confirmed cases and 6,484,136 reported deaths according to the World Health Organization (WHO) on 7 September 2022 was exceedingly catastrophic. This brought about an unexpected need for preventative and cost-effective measures to curb the devastating impact of the virus, followed by accelerated competition within the pharma giants to manufacture and dispense vaccines at an exponential rate. Non-pharmaceutical medications such as mandated face mask policies, the imposition of travel limitations and generalized disinfectant use were somewhat successful in mitigating the catastrophic effect, but the onus fell upon vaccination strategies and other medical interventions to counteract and subdue this international health threat. The need to ensure current and future pandemic preparedness, however, presents multiple hurdles, among which are equitable vaccine access and the rising trend of vaccine hesitancy at an individual and international level, which are beyond the scope of this discussion. With this review article, we seek to draw perspective on current COVID-19 virus variants, in-hand vaccine types with their mechanism of action along with their effectiveness and safety profile. We also aim to discuss substantial side effects while adding a segment on the booster dose controversy.

Recent Advances in Diagnosis and Management of Female Genital Tuberculosis.

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.

Genital tb-diagnostic algorithm and treatment.

Female genital tuberculosis (FGTB) is a common cause of infertility in India but its diagnosis remains elusive due to paucibacillary nature of disease. Traditional methods of diagnosis include demonstration of acid fast bacilli on endometrial or peritoneal biopsy or epithelioid granuloma on the biopsy or positive gene Xpert on the biopsy, but they are positive in small percentage of cases only missing diagnosis in many cases. Positive polymerase chain reaction (PCR) alone is not taken for diagnosis due to high false positivity. Diagnostic laparoscopy and hysteroscopy can detect many cases by direct demonstration of TB lesions. Composite reference standard is a useful method to diagnose FGTB. This review discusses various diagnostic modalities including endometrial or peritoneal biopsy to detect acid fast bacilli on microscopic or culture or epithelioid granuloma, role of PCR, role of radiological imaging (hysterosalpingography, ultrasound, CT scan, MRI and PET-CT scan) and role of endoscopic techniques (laparoscopy and hysteroscopy) in diagnosis of FGTB including role of composite reference standard. The International and National studies highlight the role of composite reference standard and its components like demonstration of AFB on microscopy or culture of endometrial or peritoneal biopsy or epithelioid granuloma or gene Xpert or PCR or latest tests like loop-mediated isothermal amplification (TB-LAMP) test and other newer molecular methods like Xpert Ultra for diagnosis of FGTB. It also detects role of endoscopy in FGTB and role of diagnostic algorithm for diagnosis of FGTB. Treatment is with four primary drugs (rifampicin, isoniazid, ethambutol and pyrazinamide) for two months followed by three drugs (rifampicin, isoniazid and ethambutol) daily orally for 4 months for drug sensitive FGTB. Shorter Multidrug-resistant TB (MDR-TB) regimen is given for Rifampicin resistant (RR)/MDR confined to only FGTB while longer all oral regimen is given for RR/MDR with or without additional drug resistance, HIV seropositives with FGTB or involvement of other sites or pulmonary TB (PTB) along with FGTB. Composite reference standard which combines various diagnostic modalities is a useful strategy to diagnose FGTB.

Recommendations for prenatal, intrapartum, and postpartum care during COVID-19 pandemic in India.

The pandemic of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected more than 19.7 million persons worldwide with 7 28 013 deaths till August 10, 2020. It has put an unprecedented workload on healthcare systems with special reference to labor rooms and obstetrics as deliveries cannot be stopped or postponed. Preparing their facilities using triage (COVID-positive patients, COVID-suspect patients, and COVID-negative patients) can help to better utilize the limited resources and help in prevention of spread of disease, and improve maternal and perinatal outcome. There is a need for proper training of healthcare providers for judicious use of personal protective equipment (PPE) for optimum outcome. Fortunately, the available literature suggests that there is no substantial increased risk of acquiring COVID-19 in pregnancy or its increased virulence in pregnancy and labor and there are no adverse effects on fetus and neonate with negligible fetal transmission rate. Nevertheless, utmost care is needed to manage such pregnancies, their prenatal care, and labor. This review aimed to highlight the main recommendations applied in Indian maternities for better management of pregnancy during the COVID-19 pandemic.

Obstetrics and COVID-19.

Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome corona virus 2 (SARS-Cov-2), an RNA virus which has caused pandemic in the whole world. It has put an unprecedented burden on healthcare system globally, and neither obstetricians nor labour rooms are spared as deliveries and caesarean sections cannot be postponed. There is a threat of collapse of healthcare system in maternity wards and labour rooms due to risk for transmission to healthy patients, obstetricians, midwives and other staff. It is not possible to screen all pregnant women especially in developing countries but due to asymptomatic cases, risk of infection looms large. Many countries including India have declared lockdown to stop the transmission but delivery services have to continue. Proper planning and division of the healthcare system into COVID-positive and negative areas with separate staff can help minimise the spread and preserve precious resources. Hospital staff must protect themselves by wearing personal protective equipment (PPE) in COVID-positive and suspected cases.

Female genital tuberculosis: Revisited.

Female genital tuberculosis (FGTB) is caused by Mycobacterium tuberculosis (rarely Mycobacterium bovis and/or atypical mycobacteria) being usually secondary to TB of the lungs or other organs with infection reaching through haematogenous, lymphatic route or direct spread from abdominal TB. In FGTB, fallopian tubes are affected in 90 per cent women, whereas uterine endometrium is affected in 70 per cent and ovaries in about 25 per cent women. It causes menstrual dysfunction and infertility through the damage of genital organs. Some cases may be asymptomatic. Diagnosis is often made from proper history taking, meticulous clinical examination and judicious use of investigations, especially endometrial aspirate (or biopsy) and endoscopy. Treatment is through multi-drug antitubercular treatment for adequate time period (rifampicin, isoniazid, pyrazinamide, ethambutol daily for 60 days followed by rifampicin, isoniazid, ethambutol daily for 120 days). Treatment is given for 18-24 months using the second-line drugs for drug-resistant (DR) cases. With the advent of increased access to rapid diagnostics and newer drugs, the management protocol is moving towards achieving universal drug sensitivity testing and treatment with injection-free regimens containing newer drugs, especially for new and previously treated DR cases.

Concomitant female genital tuberculosis and endometriosis.

AIMS: To demonstrate an association between female genital tuberculosis (FGTB) and endometriosis. METHODS: A total of 16 women who underwent laparoscopy (12 cases) or laparotomy (4 cases) and were found to have female genital tuberculosis and endometriosis were enrolled in this retrospective study. RESULTS: The mean age and parity were 28.2 years and 0.2, respectively. Past history of tuberculosis was present in 75% of the women (pulmonary in 50%). Menstrual dysfunction (especially oligomenorrhoea and dysmenorrhoea), constitutional symptoms, infertility, abdominal pain and lump were the main complaints. Diagnosis of FGTB was made by positive acid-fast bacilli (AFB) on microscopy, culture of endometrial aspirate, positive polymerase chain reaction (PCR), histopathological finding of epitheliod granuloma or findings of TB on laparoscopy or laparotomy. Diagnosis of endometriosis was made by laparoscopy or laparotomy. Pelvic adhesions were seen in all women, whereas frozen pelvis was seen in 7 (43.7%) women. Surgery was performed, which was laparoscopic adhesiolysis in 12 (75%), drainage of endometrioma in 12 (75%), cystectomy in 8 (50%), and total abdominal hysterectomy with bilateral salpingo-oophorectomy in 4 (25%) cases. With more then one type of (surgery in many cases). DISCUSSION: Female genital tuberculosis and endometriosis may have similar manifestations and can co-exist.

Multi drug resistant female genital tuberculosis: A preliminary report.

OBJECTIVE: Evaluation of 6 patients presenting with tubo-ovarian mass or infertility with multi drug resistant (MDR) female genital tuberculosis (FGTB). STUDY DESIGN: It was an observational study in a tertiary referral centre, India on subjects with MDR FGTB on clinical examination and investigations. All patients were given category IV drugs using kanamycin (intramuscular), levofloxacin, pyrazinamide, cycloserine, ethionamide and ethambutol (or para aminosalicylic acid [PAS] for ethambutol resistant cases) for 6 months intensive phase followed by oral levofloxacin, cycloserine, ethionamide and ethambutol (or PAS for ethambutol resistant cases) for 18 months continuation phase. Patients were evaluated for primary end points (complete cure, partial response, no response, treatment completed) and secondary end points (recurrence rate, pregnancy rate) during treatment. RESULTS: There were 2 (33.3%) primary MDR FGTB patients and 4 (66.6%) secondary MDR FGTB (three pulmonary MDR and one MDR lymphadenitis) patients. Mean age was 23.6 years. Presenting features were menstrual dysfunction in all patients (100%) especially oligomenorrhea in 3 (50%) patients, weight loss in all the patients (100%), cough with expectoration in three patients (50%), tubo-ovarian masses in five (83.3%) patients. Endometrial biopsy showed positive culture for AFB with rifampicin and isoniazid (INH) resistance in both primary MDR FGTB patients and in two secondary MDR FGTB patients who were sexually active. In secondary MDR FGTB, three pulmonary MDR patients had positive sputum AFB smear and culture, while the patient with MDR lymphadenitis had lymph node aspirate for AFB smear and culture positive with all showing resistance to rifampicin and isoniazid. Gene Xpert on endometrial biopsy or sputum was positive in 5 (83.3%) patients. Three (50%) patients (one primary and two secondary) have completed therapy while other 3 (50%) are in continuation phase. All patients are asymptomatic with one having 12 weeks ongoing successful pregnancy. CONCLUSION: MDR FGTB should be thought of in women of FGTB with tubo- ovarian masses who are not responding to first line drugs. Gene Xpert can be used in early diagnosis of MDR FGTB.

Effect of Antitubercular Therapy on Endometrial Function in Infertile Women with Female Genital Tuberculosis.

OBJECTIVE: Evaluation of anti-tubercular therapy on endometrium in Female Genital Tuberculosis. METHOD: Total of 50 women having FGTB on endometrial aspirate (positive AFB, epithelioid granuloma, positive PCR, laparoscopy or hysteroscopy findings) were enrolled. Ultrasound was performed for endometrial thickness, mean resistive index and pulsatility index before and after anti-tubercular therapy (ATT). Diagnostic hysteroscopy was performed for intra-uterine adhesions and to visualise cavity before and after ATT. RESULTS: Menstrual cycle improved after anti-tubercular therapy (ATT). Endometrial aspirate findings improved with disappearance of AFB, epithelioid granuloma and decrease in PCR (94%vs 33%). After ATT, ultrasound examination of endometrial thickness improved from 7.01±1.48 mm to 7.51±1.48 mm while mean resistive index and pulsatility index decreased from 0.729±0.304 to 0.692±0.399 and 1.180 to 1.138. With ATT, improvement was seen in hysteroscopic findings with normal looking cavity increasing from 18(36%) to 34(72.1%) and pale looking cavity decreasing from 20(42.5%) to 8(16.8%). Before ATT, prevalence of intrauterine adhesions was 62% which decreased to 28.7% after ATT. Improvement was significant only in grade I adhesions from 34% to 2.1%, (p<0.001). There was no improvement in higher grade of intrauterine adhesions with ATT with grade II (6% vs 4.2%) and grade 2a (4% vs 2.1%), grade III being (2% vs 2.1%), grade II a (4% vs 4.2%), grade Va (4% vs 4.2%) and grade Vb (8% vs 10.6%) before and after ATT respectively. CONCLUSION: Early ATT improved menstrual cycle, endometrial thickness and reduced incidence of grade I adhesions. Advanced stages did not show any improvement.