Genital footprints of extragenital tuberculosis in infertile women: Comparison of various diagnostic modalities.

BACKGROUND: Genital tuberculosis (TB) continues to remain an important cause of infertility in women, especially in developing countries. It is mostly consequent to a primary infection elsewhere in the body. The diagnosis is challenging, considering its paucibacillary nature. Although there are many studies on association of genital tuberculosis with infertility, there is paucity of literature on impact of extragenital tuberculosis on fertility of women through involvement of female reproductive organs. The various diagnostic modalities available have limitations and quest is ongoing for the best diagnostic test. METHOD: This was a prospective observational study conducted at the infertility clinic of a tertiary care health facility where 60 infertile women with either tubal factor or unexplained infertility with or without past history of extragenital tuberculosis were enrolled as study subjects or controls respectively. Mantoux test was performed in all women and diagnostic laparo-hysteroscopy was performed in all women to look for any evidence of uterine and/or tubal damage. The peritoneal fluid was sent for GeneXpert and Liquid culture for mycobacterium tuberculosis. Results of Mantoux test, GeneXpert and liquid culture were compared with the laparohysteroscopic findings. RESULT: Of the thirty infertile women in the study group, 27/30 (90%) had a history of pulmonary tuberculosis and 3/30 (10%) had history of tubercular cervical lymphadenopathy. It was observed that Mantoux test was positive (induration >10 mm) in 27/30 (90%) of women in the study group as compared to only 4/30 (13.3%) controls. Abnormal hysteroscopic findings were documented in 26.6% (8/30) study group women as compared to 6.6% (2/30) women in the control group. Similarly, 60% (18/30) of women in the study group had abnormal laparoscopic findings compared to 33% (10/30) in the control group. Seven out of thirty (23.3%) women were positive for GeneXpert in the study group compared to only 1/30 (3.3%) in the control group. Similarly, liquid culture was positive in 6/30 (20%) of women in the study group as compared to 1/30 (3.3%) in the control group. All the above differences were statistically significant. We observed that the sensitivity of Mantoux test (75.8%) stand alone was higher than the other tests combined (50%). However, specificity and positive predictive value (PPV) increases markedly (up to 100%) to when all the three tests are combined. CONCLUSION: The authors conclude that all women presenting with infertility should be screened for a past history of tuberculosis and actively worked up for genital tuberculosis in case the history is positive. The various available tests (Mantoux test, GeneXpert and liquid culture) have their limitations for the diagnosis of genital tuberculosis. Thus an approach of early resort to laparohysteroscopy in suspected patients is desirable so that definitive management may be instituted timely and promptly.

Evidence of sexual transfer of mycobacteria from male to female partners reporting to an IVF clinic.

Female genital tuberculosis (GTB) contributes significantly to infertility in low- and middle-income countries. Dissemination of infection from pulmonary and extrapulmonary sites is the major reason for causation of GTB. Additionally, sexual transmission of GTB from male partners has been reported. We selected 81 couples desiring babies from an in vitro fertilization clinic. We used multiplex-PCR for mycobacterial detection in semen of males, in the endometrium of their female counterparts and in the products of conception (POC) from miscarriage. Data interpretation shows that these pregnancies failed owing to sexual transmission of mycobacteria. We noticed by multiplex PCR that mycobacterial infestation in the female can take place in either endometrium or POC from asymptomatic males harbouring mycobacteria in their semen. Therefore, we propose sexual transfer of mycobacteria to be a probable cause of miscarriage. Thus, we suggest multiplex PCR based screening of semen for all males of the couples attempting successful childbirth.

Genital tuberculosis role in female infertility in Portugal.

INTRODUCTION: Genitourinary tuberculosis is the fourth most common cause of extrapulmonary tuberculosis, although often underestimated by clinicians due to its rare and non-specific symptoms. One of the disease's complications is infertility. Although Portugal is one of the European countries with the highest prevalence of tuberculosis, its impact on Portuguese female fertility is unknown. With this study, we intend to evaluate the prevalence of genital tuberculosis, its presenting symptoms, and pregnancy outcomes in infertile women followed in a Portuguese tertiary hospital. METHODS: Retrospective and descriptive study, performed using an electronic database and consultation of clinical files. Studied population: infertile women followed from 2000 until 2019 at the reproductive unit of a Portuguese tertiary hospital, who underwent endometrial biopsy/curettage in the context of their etiological investigation. The diagnosis of genital tuberculosis was based on histological criteria. RESULTS: Over the 19 years, 2653 endometrial specimens were analyzed. Pathological evaluation was positive for tuberculosis in 19 cases (0.72%). There was a decrease in new diagnoses throughout the observation period. CONCLUSION: Despite being one of the European countries with the highest prevalence of tuberculosis, genital TB does not appear to have a significant impact on the etiology of female infertility in Portugal. Nevertheless, it is a diagnosis to be considered in selected patients.

Endometritis granulomatosa por tuberculosis en mujer postmenopaúsica / Granulomatous tuberculosis endometritis in a posmenopausal woman

INTRODUCCIÓN: La tuberculosis (TBC) genital es una infección relativamente poco frecuente en la mujer. Afecta principalmente a mujeres menores de 40 años, y el motivo de consulta más usual es la esterilidad, de ahí la importancia de su diagnóstico precoz. CASO CLÍNICO clínico: Se presenta el caso de una paciente con dolor pélvico crónico que acude a nuestras consultas para valoración. Durante el estudio se toma biopsia dirigida de la cavidad endometrial diagnosticándose la presencia de granulomas no necrotizantes. Posteriormente se realiza un cultivo microbiológico que resulta positivo para micobacterias y se determina el DNA, mediante reacción en cadena de la polimerasa, de mycobacterium tuberculosis, como causante del cuadro. DISCUSIÓN: El diagnóstico definitivo de TBC requiere el aislamiento en cultivo del bacilo de Koch, aunque en los casos de TBC genital, al ser una entidad paucibacilar, puede no resultar positivo. En éste caso, sería suficiente el diagnóstico de presunción basado en la sospecha clínica y el hallazgo histológico de granulomas. CONCLUSIÓN: La tuberculosis genital es una entidad poco frecuente en nuestro medio, aunque es una causa importante de infertilidad femenina y su predominio generalmente se subestima debido a la naturaleza paucisintomática de la misma. El diagnóstico temprano y el tratamiento multidisciplinar son fundamentales.

INTRODUCTION: Genital tuberculosis (TB) is a relatively rare afection in women. It mainly affects women younger than 40 years, and the most frequent reason for consultation is sterility, therefore early diagnosis is important. CLINICAL CASE: We presented the case of a patient with chronic pelvic pain who comes to our consultations. During the study, we take an endometrial biopsy diagnosing the presence of non-necrotizing granulomas. Finally, we determined the mycobacterium tuberculosis DNA through the polymerase chain reaction and positive microbiological culture, as the cause of pathology. DISCUSSION: The definitive diagnosis of TB requires the isolation in culture of the Koch bacillus, although in genital TB cases, as it is a paucibacillary entity, it may not be positive. In this case, the presumptive diagnosis based on clinical suspicion and the histological granulomas would be enough. CONCLUSIONS: Genital tuberculosis is a rare entity in our environment, although it is an important cause of female infertility and its prevalence is generally underestimated due to its paucisymptomatic nature. Early diagnosis and multidisciplinary treatment are essential.

Role of Laparoscopy in the Diagnosis of Genital TB in Infertile Females in the Era of Molecular Tests.

STUDY OBJECTIVE: To assess diagnostic value of polymerase chain reaction (PCR) in endometrial aspirates (EAs) in comparison with conventional tests for diagnosis of female genital tuberculosis (TB) and to find agreement between EA PCR done for endometrial TB and laparoscopic findings of pelvic TB in women with unexplained infertility. DESIGN: Prospective observational cohort study. SETTING: Tertiary care hospital. PATIENTS: A total of 732 infertile females screened and 385 enrolled to undergo procedure to obtain EAs. INTERVENTIONS: EAs were tested by conventional tests (histopathology, acid-fast bacilli, Lowenstein-Jensen staining, liquid culture) and PCR for Mycobacterium tuberculosis. Patients with positive conventional tests were started on antitubercular treatment (ATT). Patients with negative conventional tests underwent laparohysteroscopy irrespective of PCR results to assess changes of tubercular infection in the pelvis. Peritoneal washings were also sent for liquid culture and PCR for TB, and suspicious lesions were biopsied at laparohysteroscopy. Findings at laparoscopy upgraded the diagnosis in these women. EAPCR results were analyzed to find agreement with the findings at laparoscopy. MEASUREMENTS AND MAIN RESULTS: Conventional tests were positive in 8 of 385 (2%) patients. PCR was positive in 58.1% (n = 224) of endometrial samples, with sensitivity of 62.5% (95% confidence interval [CI], 24.49-91.48), specificity of 41.91% (95% CI, 36.88-47.07), positive predictive value of 2.23% (95% CI, 1.31-3.78), negative predictive value of 98.14% (95% CI, 95.53-99.24), and a diagnostic accuracy of 42.34% (95% CI, 37.35-47.45) with conventional tests. A total of 265 patients underwent laparoscopy, of whom 165 were PCR positive and 100 were PCR negative. Laparoscopic findings suggestive of TB were found in 39.3% of patients who were PCR positive and 9% of patients who were PCR negative. Kappa agreement was 0.25, suggesting fair agreement between PCR and laparoscopy. CONCLUSION: PCR as a stand-alone diagnostic test for endometrial TB is not justified to confirm diagnosis and initiate ATT. The addition of laparohysteroscopy improves diagnostic yield for genital TB. Referring patients with a suspicion of female genital TB to tertiary care for 1-time laparoscopy is better than initiating ATT solely on the basis of PCR results.

Role of microbiological tests in diagnosis of genital tuberculosis of women with infertility: A view.

OBJECTIVE: India is a country sharing one fourth of the global incidence of tuberculosis. It is much easier to diagnose pulmonary cases, but challenges are with extrapulmonary cases. Genital tuberculosis is considered as an important cause of infertility in young females in India and difficult to diagnose. It requires incorporation of different modalities that should correctly, timely and rapidly diagnose the case. METHODS: This study was conducted retrospectively for a period of 12 months on 438 endometrial samples from females with history of infertility. Three modalities namely Ziehl-Neelsen staining, Automated liquid culture and Nucleic acid amplification technique (TB-PCR) were compared and their sensitivity in diagnosis of genital tuberculosis was ascertained. RESULTS: Out of 438 samples, 18 samples were found positive with at least one modality. TB-PCR positivity was 3.6% (16 cases) in comparison to culture where positivity was 1.59% (7 cases). Five samples were found culture and TB-PCR positive and only one sample was positive by all three diagnostic tests. CONCLUSION: Infertility in young female per se is usually heart breaking and distressing. Therefore, it is essential to diagnose and treat the cases of genital tuberculosis before irreversible damage of tube may happen. Although, advancement in diagnostic field is there from microscopy to molecular method, but still diagnosis of genital tuberculosis is challenging. Correct diagnosis prevents young female from mental trauma and toxicity of anti-tuberculosis drugs given on suspicion in high prevalence country like India.

Conventional polymerase chain reaction and amplification refractory mutation system-multi-gene/ multi-primer PCR in the diagnosis of female genital tuberculosis.

This review mainly summarizes disease, immune-pathology and the clinical usefulness, advances, potential applications and limitations of new, cutting-edge technology (MG/MP-PCR and/or ARMS-MG/MP-PCR) in the detection of female genital tuberculosis (FGTB) disease and gene polymorphism among infertile patients. The investigation was set in the Department of Zoology, Osmania University and National Institute of Nutrition, Hyderabad, India. Desired articles were critically reviewed and analysed. Keywords and NET searches were conducted in all electronic databases starting from September, 2006. Full-text English-language reviews and research articles describing FGTB, infertility, gene polymorphism, conventional polymerase chain reaction (PCR) and multigene (MG)/multiprimer (MP)-PCR were included. The current review provides a comprehensive overview on the PCR and types (multiplex, nested, RT etc.) including the reagents, cycling conditions and pitfalls in the detection of FGTB disease and gene polymorphism among infertile patients. It provides limited information on MG/MP-PCR. At present, conventional PCR, MG/MP-PCR and/or amplification refractory mutation system (ARMS)-MG/MP-PCR have emerged as scientific innovations and perform significant function in medical research, mutational analysis and clinical investigations. This review admits that MG/MP-PCR and/or ARMS-MG/MP-PCR has the capacity to diagnose disease rapidly and to genotype a large number of samples. MG/MP-PCR and/or ARMS-MG/MP-PCR are considered as simple, reliable, non-isotopic, low-cost, fast, accurate and relatively easy-to-perform procedure. This review suggests that this method needs to be critically evaluated using huge number of clinical samples occurring across the world and then can be accredited for clinical utilization.

Congenital tuberculosis after in vitro fertilization: suggestion for tuberculosis tests in infertile women in developing countries.

Congenital tuberculosis (CTB) after in vitro fertilization (IVF) is a major new problem in developing countries. Only 16 cases of CTB after IVF have been reported, and no tuberculosis (TB) tests were performed before IVF in these cases. However, on the basis of data in the literature and from the World Health Organization, the incidence of CTB has been substantially underestimated. We describe two cases of CTB after IVF in detail in our center and provide new insight into the important issue of controlling TB vertical transmission in developing countries. Performing an early diagnosis of CTB, mostly based on evidence of maternal infection and a high index of clinical suspicion, is a challenge. However, most mothers have no symptoms of TB infection during prepartum, and infertility may be the only symptom. Infertility caused by genital TB is common in countries with a high TB burden, and IVF is considered to be an effective treatment to improve their fertility. Therefore, this may lead to more CTB cases without thorough TB tests before IVF. We suggest that thorough TB tests should be conducted in infertile women before IVF to prevent CTB.

Endometrial tuberculosis among patients undergoing endometrial biopsy at Tikur Anbesa specialized hospital, Addis Ababa, Ethiopia.

BACKGROUND: Female genital tuberculosis (FGTB) is known to cause severe tubal disease leading to infertility and its incidence closely parallels with the overall prevalence of tuberculosis (TB) in a community. Its magnitude is underreported because diagnosis is difficult and requires invasive techniques. In this study we determined the prevalence of endometrial tuberculosis and characterized isolates among women who underwent endometrial biopsy for evaluation of various conditions at a Tikur Anbessa Specialized Hospital (TAHS), Addis Ababa, Ethiopia. METHODS: A cross sectional study was conducted on 152 consecutive gynecologic patients who underwent endometrial biopsy for different gynecologic diseases. Endometrial tissue taken for routine histopathology examination was shared after informed consent was obtained from the patient and subjected to polymerase chain reaction (PCR) and culture for Mycobacterium tuberculosis (Mtb). RESULTS: The prevalence of endometrial TB in this study by IS1081PCR was 4.6% (7/152) while culture proven endometrial TB was 2.6% (4/152). However, histological examination identified only 2/152 (1.3%) endometrial tuberculosis. While all culture proven TB samples were also PCR positive for Mtb, only one histologic proven endometrial TB was culture and PCR positive. All of the four isolates by culture were M. tuberculosis. CONCLUSION: This study has shown that the magnitude of endometrial TB is fairly high in gynecologic patients visiting outpatient departments for various complaints and PCR detects more cases than culture or Histopathology.

Multiplex PCR from Menstrual Blood: A Non-Invasive Cost-Effective Approach to Reduce Diagnostic Dilemma for Genital Tuberculosis.

AIM: Genital tuberculosis (GTB) is a potent contributor to irreversible damage to the reproductive system and infertility in females. As no gold standard diagnostic tool is yet available, clinical suspicion and relatively insensitive approaches such as histopathology, laparoscopy and hysterosalpingogram are currently critical determinants in the diagnosis of GTB. Although a polymerase chain reaction (PCR)-based assay using endometrial tissue seems promising, sampling does require an invasive procedure. OBJECTIVE: We hypothesized that menstrual blood may provide an alternate non-invasive source of samples for PCR-based GTB diagnosis. METHODS: We enrolled 195 women with primary infertility in whom GTB was suspected. We obtained ethics committee approval from our institution and written informed consent from subjects. Endometrial tissue and menstrual blood was collected from the subjects and culture, histopathology, and multiplex PCR with both sample type was performed for each subject. RESULTS: The sensitivity and specificity of multiplex PCR was, respectively, 90.2 and 86.1% for menstrual blood, 95.8 and 84.3% for endometrial tissue, and 64.8 and 93.2% for histopathology staining. CONCLUSIONS: A strong clinical suspicion aided with multiplex PCR using menstrual blood may significantly reduce the diagnostic dilemma for GTB diagnosis in a non-invasive, sensitive, rapid, and cost-effective manner.

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.

Female genital tuberculosis and infertility: serial cases report in Bandung, Indonesia and literature review.

BACKGROUND: Female genital tuberculosis (FGTB) is a Mycobacterium infection in the reproductive organs which often leads to infertility. FGTB is either asymptomatic or causes uncharacteristic clinical presentations, making an early diagnosis is challenging. Our aims were to evaluate the clinical presentations, the process to confirm the diagnosis and followed-up the patients who had undergone laparoscopy at our center. FGTB has been reported from many countries, but has never been reported from Indonesia. Here we present case studies to document the presence of FGTB in Indonesia. CASES PRESENTATION: There were three patients admitted to our center; two patients were admitted with irregular menstrual cycle as their chief complaint, while one patient came due to infertility. The results from laparoscopy were suggestive of FGTB; including the presence of caseating granulomas surrounded by epithelioid cells, lymphocytes, plasma cells, and Langhans giant cells. Additionally, PCR testing confirmed presence of MTB. Subsequent to diagnosis, continuous TB medications was administered with excellent clinical outcome in two patients (pregnant in 18 months after under gone laparoscopy). The infertile patient remain in one of the treated patient above. CONCLUSION: In infertile patients who live in countries where Tuberculosis is an endemic disease, such as Indonesia, a comprehensive history taking, along with ultrasonography results can be used to diagnose FGTB. Confirmation of this diagnosis can be achieved through polymerase chain reactions result. Timely diagnosis and treatment are imperative to prevent any permanent injury to patient's reproductive organs.

Genital tuberculosis in females.

The morbidity and mortality due to tuberculosis (TB) is high worldwide, and the burden of disease among women is significant, especially in developing countries. Mycobacterium tuberculosis bacilli reach the genital tract primarily by haematogenous spread and dissemination from foci outside the genitalia with lungs as the common primary focus. Genital TB in females is a chronic disease with low-grade symptoms. The fallopian tubes are affected in almost all cases of genital TB, and along with endometrial involvement, it causes infertility in patients. Many women present with atypical symptoms which mimic other gynaecological conditions. A combination of investigations is needed to establish the diagnosis of female genital TB (FGTB). Multidrug anti-TB treatment is the mainstay of management and surgery may be required in advanced cases. Conception rates are low among infertile women with genital TB even after multidrug therapy for TB, and the risk of complications such as ectopic pregnancy and miscarriage is high. More research is needed on the changing trends in the prevalence and on the appropriate methods for diagnosis of FGTB.

Congenital tuberculosis in an extremely preterm infant conceived after in vitro fertilization: case report.

BACKGROUND: Congenital tuberculosis is a rare manifestation of tuberculosis. The diagnosis is often delayed, especially in preterm neonates because of the non-specific clinical presentation and the lack of awareness of maternal disease prior to pregnancy. CASE PRESENTATION: We report a case of congenital tuberculosis in an infant born at 24 weeks of gestation to a mother who presented with uncontrolled seizures during preterm labor. Maternal diagnosis was initially made by placental pathology, and later confirmed by isolation of Mycobacterium tuberculosis in urine, gastric aspirates and sputum. Full screening was performed on the newborn infant, and both mother and infant were successfully treated for tuberculosis with a four drug regimen. CONCLUSION: Pregnancy can exacerbate latent tuberculosis and women originating from endemic areas are especially susceptible. The best way to prevent congenital tuberculosis is to have a high index of suspicion and identify and treat tuberculosis in pregnant women.

NMR-based metabonomics for understanding the influence of dormant female genital tuberculosis on metabolism of the human endometrium.

STUDY QUESTION: Does investigation of metabolic perturbations in endometrial tissue of women with dormant genital tuberculosis (GTB) during the window of implantation (WOI) assist in improving the understanding of endometrial receptivity? SUMMARY ANSWER: In dormant GTB cases significant alterations in endometrial tissue metabolites occur, largely related to energy metabolism and amino acid biosynthesis in dormant GTB cases. WHAT IS KNOWN ALREADY: As an intracellular pathogen, Mycobacterium tuberculosis strongly influences the metabolism of host cells causing metabolic dysregulation. It is also accepted that dormant GTB impairs the receptive status of the endometrium. Global metabolic profiling is useful for an understanding of disease progression and distinguishing between diseased and non-diseased groups. STUDY DESIGN, SIZE, DURATION: Endometrial tissue samples were collected from patients reporting at the tertiary infertility care center during the period September 2011-March 2013. Women having tested positive for GTB were considered as the study group (n = 24). Normal healthy women undergoing sterilization (n = 26) and unexplained infertile women with repeated IVF failure (n = 21) volunteered to participate as controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial tissue samples were collected 6-10 days after confirmation of ovulation. PCR and BACTEC-460 culture were used for diagnosing GTB. Proton nuclear magnetic resonance (1H NMR) spectra of tissue were recorded using a 700 MHz Bruker Avance AV III spectrometer. Following phase and baseline correction of all NMR spectra by Bruker Topspin 2.1 software, spectral peak alignment of the data was performed. Multivariate analysis was applied to all spectra and individual metabolites identified and multiple correlation analysis was performed. MAIN RESULTS AND THE ROLE OF CHANCE: Leucine, isoleucine, acetate, lactate, glutamate, glutamine, methionine, lysine, creatine, glycogen, glycine, proline and choline were found to be significantly increased (P < 0.05) in endometrial tissue of women with dormant GTB compared with unexplained infertile women with repeated implantation failure. Valine, citrate, succinate and aspartate were also observed to be significantly up-regulated (P < 0.01). Furthermore, a significant decrease in glucose (P < 0.05), threonine (P < 0.05), tyrosine (P < 0.01) and phenylalanine (P < 0.0001) was observed in women with dormant GTB. Pearson's correlation analysis between the expression of various endometrial receptivity markers and metabolites showed a significant negative correlation (-0.236 to -0.545, P < 0.05). Also, the metabolites were positively correlated with endometrial receptivity markers (0.207 to 0.618, P < 0.05). LIMITATIONS, REASONS FOR CAUTION: It is often difficult to diagnose dormant GTB because it tends to exist without any clinical signs or symptoms. In addition, the diagnosis of GTB by culture remains a challenge due to low detection rates and its paucibacillary nature. Testing for prostate-specific antigen or the Y chromosome in order to account for the possible influences of recent exposure to semen on endometrial metabolism would be important. WIDER IMPLICATIONS OF THE FINDINGS: The metabolic changes associated with the dormant tubercle infection are of potential relevance to clinicians for the treatment of dormant GTB-related infertility. STUDY FUNDING/COMPETING INTERESTS: Government of India, Indian Council of Medical Research. There are no conflicts of interest.

Investigation of Toll-Like Receptor-2 (2258G/A) and Interferon Gamma (+874T/A) Gene Polymorphisms among Infertile Women with Female Genital Tuberculosis.

BACKGROUND: Toll-like receptor 2 (TLR2) and interferon-gamma (IFN-γ) coordinate with a diverse array of cellular programs through the transcriptional regulation of immunologically relevant genes and play an important role in immune system, reproductive physiology and basic pathology. Alterations in the functions of TLR2 2258G (guanine)/ A, IFN-γ (+874T/A) and signalling molecules that result from polymorphisms are often associated with susceptibility or resistance, which may, in turn, establish the innate host response to various infectious diseases. Presently, we proposed to investigate the risk of common single nucleotide polymorphism (SNP) of TLR2 and IFN-γ genes, for their effect on infertility in women with female genital tuberculosis (FGTB) and healthy women as controls. METHODOLOGY/PRINCIPAL FINDINGS: Genotyping of TLR2 and IFN-γ gene polymorphisms was performed by amplification refractory mutation system multi-gene/multi-primer polymerase chain reaction followed by restriction fragment length polymorphism in 175 FGTB patients and 100 healthy control women (HCW). The TLR2 polymorphism [adenine (A) allele] was observed in 57.7 and 58.0% of FGTB patients and HCW, respectively. The IFN-γ (+874T/A) polymorphism (A allele) was significant in 74.3 and 71.0% of FGTB patients and HCW, respectively, while the odds ratios for the AA and TA genotypes for predisposition of FGTB were found to be 0.304 and 1.650 in HCW, respectively. The SNP of TLR2 was not associated with FGTB but the SNP of IFN-γ was found to be associated with mycobacteria infections and to induce infertility. CONCLUSIONS/SIGNIFICANCE: At present, we hypothesize that infertile women with FGTB and HCW without tuberculosis (TB) have identical frequency of TLR variants, which may be adequate in the production of IFN-γ in response to Mycobacterium tuberculosis infections. Thus, the study appears to be the first of its kind reporting a mutation in the IFN-γ gene [+874 T (thymine) to A] responsible for susceptibility to TB infections and further inducing infertility.

Intrauterine Tuberculosis Manifesting as Acute Chorioamnionitis: A Case Report and Review of the Literature.

Congenital tuberculosis involving the placenta is an infrequent diagnosis, and the typical features of tuberculous placentitis involve a granulomatous reaction, reflecting a delayed hypersensitivity immune response in the host. However, the first reaction of the placenta to organisms hematogenously transmitted from the maternal circulation typically involves the innate immune response, manifesting as an acute neutrophilic villitis or intervillositis or both. This acute pattern of response to mycobacteria has only been documented rarely. We present a case of acute mycobacterial infection occurring in a preterm female with 28-weeks gestation, who was delivered by cesarean section because of fetal distress and who was subsequently confirmed to have congenital tuberculosis. The placenta showed an acute chorioamnionitis associated with acid-fast bacilli consistent with Mycobacteria tuberculosis. The mother was found to have a necrotizing granulomatous deciduitis, and that was postulated to have resulted in the direct spread of mycobacteria to the amniotic cavity. Thus, our case extends the acute placental response to mycobacteria to include chorioamnionitis. Although extremely rare, mycobacteria should be considered in the differential diagnosis of infectious agents causing acute chorioamnionitis, especially in geographic areas where tuberculosis is more prevalent.

[Implication of laparoscopy in diagnostics of genital tb among women through cytohistological testing of bioptic specimen].

Diagnostics of genital TB among women is a serious challenge because of the absence of specific clinical manifestation and difficulty to obtain material for bacteriological verification of the pathogen. All the cases with ascites and masses in pelvic cavity must undergo thorough testing to exclude tuberculosis. The present article describes 14 suspect cases of genital TB, where along with the mandatory clinical diagnostic studies (including PCR of ascites and bacteriological testing for TB, also on carcinoma of CA-125 ovary) they have conducted laparoscopy, with further cytological and bacteriological testing of bioptic sample. This method allowed us to diagnose genital and abdominal tuberculosis among women in 85,7% of cases through cytologic and histologic testing and to exclude ovarian carcinoma. Effectiveness of laparoscopy has been confirmed in diagnostics of genital and abdominal TB.

Cervical tuberculosis masquerading as cancer cervix: a report of three cases.

Tuberculosis is still frequently observed in third world countries like Africa and Asia. Here we report three cases of genital tuberculosis with variable presentations. First case was a lady of reproductive age group who presented with polymenorrhea and post-coital bleeding with unhealthy cervix. Histopathology of cervical tissue revealed tubercular cervicitis. Second and third cases presented with different complaints like discharge per vaginum, post-coital bleeding and pain in lower abdomen with growth over the cervix. Cervical biopsy was inconclusive of tuberculosis but endometrial tissue sampling for TB PCR was positive. This shows that newer diagnostic marker test can help us to detect secondary genital tuberculosis.