Cross sectional study to evaluate microbiological spectrum of RTI/STI and co-infections among women with cervicitis or cervico-vaginitis from a community clinic in Mumbai

Cervicitis is an inflammatory condition of cervix, when presented along with vaginal discharge; it is termed as cervico-vaginitis. These can be infective, hence important to diagnose due to risk of spreading to upper genital tract. This cross-sectional study was undertaken to evaluate the microbiological spectrum in cervicitis or cervico-vaginitis among 100 sexually active women by Gram stain and Multiplex Real time polymerase chain reaction. Bacterial vaginosis 21(21%) was the most common RTI. Among STIs, genital mycoplasmas were the predominant infections hence further research is required to understand their pathogenesis.     

Chlamydia trachomatis seropositivity is associated both with stillbirth and preterm delivery

The cause of stillbirth and preterm delivery is often unknown. We studied the prevalence of Chlamydia trachomatis antibodies in mothers with stillbirth and preterm labor. Serum specimens from 72 mothers with stillbirth after the 21st gestational week, and from 48 mothers with preterm delivery between gestational weeks 23 and 29, both from the greater Helsinki area, and cord blood from 96 consecutive liveborn deliveries at the Department of Obstetrics and Gynecology, the University of Helsinki, were studied for antibodies to C. trachomatis immunotypes CJHI, GFK and BED by microimmunofluorescence test. The prevalence of C. trachomatis antibodies was highest, 33.3%, in mothers with stillbirth, 18.8% in mothers with preterm delivery, and 10.4% in cord blood. The IgM seropositivity rate was high among mothers with preterm delivery (8.3%). We conclude that C. trachomatis IgG antibodies are frequently detected in sera from mothers with stillbirth, suggesting past infection, while mothers with preterm delivery often have serum IgM antibodies, suggesting of acute infection.     

Bacterial vaginosis. Transmission, role in genital tract infection and pregnancy outcome: an enigma

Whether bacterial vaginosis (BV) is acquired from an endogenous or an exogenous source is subject to controversy. Despite findings of an association between sexual behaviour and BV, some data indicate that BV is not a sexually transmitted infection in the traditional sense, while other data indicate that BV is an exogenous infection. A third aspect of BV is its tendency to go unnoticed by affected women. All of this will have a strong impact on how physicians view the risks of asymptomatic BV. This review focuses on whether or not BV should be regarded as a sexually transmitted infection (STI), its role in postoperative infections and pelvic inflammatory disease (PID), and on whether or not treatment of BV during pregnancy to reduce preterm delivery should be recommended. The reviewed studies do not lend unequivocal support to an endogenous or exogenous transmission of the bacteria present in BV. For women undergoing gynaecological surgery such as therapeutic abortion, the relative risk of postoperative infection is clearly elevated (approx. 2.3-2.8). A weaker association exists between BV and pelvic inflammatory disease. Data on treatment of BV as a way of reducing preterm delivery are inconclusive and do not support recommendations for general treatment of BV during pregnancy. The discrepant associations between BV and preterm birth found in recent studies may be explained by variations in immunological response to BV. Genetic polymorphism in the cytokine response--both regarding the TNF alleles and in interleukin production--could make women more or less susceptible to BV, causing different risks of preterm birth. Thus, studies on the vaginal inflammatory response to microbial colonization should be given priority.     

Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma

Allergen-reactive T helper type-2 (Th2) cells and proinflammatory cytokines have been suggested to play an important role in the induction and maintenance of the inflammatory cascade in allergic asthma. We compared the plasma concentrations of novel proinflammatory cytokines IL-17 and IL-18, other proinflammatory cytokines IL-6 and IL-12, Th2 cytokines IL-10 and IL-13, and intracellular interferon-gamma (IFN-gamma) and IL-4 in Th cells of 41 allergic asthmatics and 30 sex- and age-matched health control subjects. Plasma cytokines were measured by enzyme-linked immunosorbent assay. Intracellular cytokines were quantified by flow cytometry. Plasma IL-18, IL-12, IL-10, IL-13 concentrations were significantly higher in allergic asthmatic patients than normal control subjects (IL-18: median 228.35 versus 138.72 pg/ml, P < 0.001; IL-12: 0.00 versus 0.00 pg/ml, P = 0.001; IL-10: 2.51 versus 0.05 pg/ml, P < 0.034; IL-13: 119.38 versus 17.89 pg/ml, P < 0.001). Allergic asthmatic patients showed higher plasma IL-17 and IL-6 concentrations than normal controls (22.40 versus 11.86 pg/ml and 3.42 versus 0.61 pg/ml, respectively), although the differences were not statistically significant (P = 0.077 and 0.053, respectively). The percentage of IFN-gamma-producing Th cells was significantly higher in normal control subjects than asthmatic patients (23.46 versus 5.72%, P < 0.001) but the percentage of IL-4 producing Th cells did not differ (0.72 versus 0.79%, P > 0.05). Consequently, the Th1/Th2 cell ratio was significantly higher in normal subjects than asthmatic patients (29.6 versus 8.38%, P < 0.001). We propose that allergic asthma is characterized by an elevation of both proinflammatory and Th2 cytokines. The significantly lower ratio of Th1/Th2 cells confirms a predominance of Th2 cells response in allergic asthma.     

Decreased cervicovaginal production of both IgA1 and IgA2 subclasses in women with AIDS

Paired sera and cervicovaginal secretions from 35 HIV-1-infected women representing different CDC stages of HIV infection were evaluated for total IgA, IgA1 and IgA2, for IgA, IgA1 and IgA2 to gp160, and for albumin. Age-matched healthy women (n= 45) served as controls. The secretion rates of total IgA, IgA1 and IgA2 were evaluated by calculating their relative coefficients of excretion by reference to albumin. In HIV-infected women, total IgA1 and IgA2 in sera and in cervicovaginal secretions increased proportionately as early as stages II + III and more markedly at stage IV. By contrast, the secretion rates of total IgA, IgA1 and IgA2 were markedly reduced in AIDS women, the IgA2 secretion rate decreasing significantly as early as stages II +III. This apparent discrepancy was probably the result of increased transudation of serum-borne immunoglobulins into the vaginal cavity, since albumin levels in cervicovaginal secretions increased significantly according to the stages of disease. HIV-reactive IgA antibodies in serum, as in cervicovaginal secretions, were principally found within the IgA 1 subclass. In women at stage IV, a high local production of IgA1 to gp160 occurred in spite of the impairment of cervicovaginal IgA synthesis, probably because of marked genital HIV replication at advanced stages.     

Chlamydia trachomatis infection in mothers with preterm delivery and in their newborn infants

We studied Chlamydia trachomatis infection in mothers with preterm delivery and intrauterine transmission of the infection to their offspring. Forty-one mothers with preterm labour and their newborn infants (n=50) were studied for the presence of C. trachomatis infection using microimmunofluorescence test for detection of serum antibodies against C trachomatis and polymerase chain reaction for detection of C. trachomatis-specific DNA in mucosal swabs. Antibodies to C trachomatis were found in serum of 12 mothers (29%). Five of fourteen mothers had C. trachomatis DNA in cervical specimens. Eighteen neonates were born to the 14 mothers with positive serology and/or C. trachomatis DNA. C. trachomatis DNA was detected in specimens from 10 of the 18 neonates (55.5%). Three of the available cord blood samples contained C trachomatis IgM antibodies. Our results strongly suggest that mothers and their preterm babies may benefit from screening for active C. trachomatis infection.     

Intercellular adhesion molecule-1 (ICAM-1) in cervicovaginal fluid of women presenting with preterm labor: predictive value for preterm delivery

PROBLEM: Clinically useful tests for the prediction and diagnosis of preterm labor and delivery remain to be established. We have hypothesized that soluble intercellular adhesion molecule-1 (sICAM-1) in the cervicovaginal fluid of women with preterm labor may be a useful diagnostic tool. METHOD OF STUDY: The cervicovaginal fluid of 103 women between 24(0) and 33(6) weeks gestation with preterm contractions and intact membranes was assayed for sICAM-1. RESULTS: Elevated sICAM-1 concentrations predicted short intervals to delivery (area under receiver operator characteristic (ROC) curves, 0.70-0.72 for delivery within 3, 7 and 10 days), with high specificity. Characteristics for delivery within 3 days at a 3 ng/mL threshold for a positive test were sensitivity 33.3%, specificity 98.9%, and positive and negative predictive values of 75.0% and 93.9%, respectively. Predictive ability was independent of and complementary to that of fetal fibronectin (fFN). CONCLUSIONS: Measurement of sICAM-1 in cervicovaginal fluid has potential as a predictor of preterm delivery in women with symptoms of preterm labor, particularly in conjunction with fFN testing.     

Elevated interleukin-8 in cervical mucus as an indicator for treatment to prevent premature birth and preterm, pre-labor rupture of membranes: a prospective study

PROBLEM: We investigated whether cervical shortening and high interleukin (IL)-8 in cervical mucus were valuable indications for treatment to prevent premature birth and preterm, pre-labor rupture of membranes (pPROM). METHOD OF STUDY: Pregnant women were divided into group A, in which neither cervical IL-8 nor cervical length was measured in the middle trimester; and groups B and C, in which cervical length and cervical IL-8 were measured, and bed rest or cerclage was performed when cervical shortening was detected. In group B, vaginal washing with povidone iodine and insertion of chloramphenicol vaginal tablets were carried out in women with IL-8 elevations. RESULTS: In group B, duration of pregnancy was significantly prolonged compared with group A and C, and occurrence of pPROM was significantly lower. No significant differences were found in those rates between groups A and C. CONCLUSION: Successful treatment for women with IL-8 elevations in cervical mucus decreased rates of premature birth or pPROM.     

Elevated serum levels of Interleukin‐37 are associated with inflammatory cytokines and disease activity in rheumatoid arthritis

Interleukin‐37 (IL‐37) is closely associated with several inflammatory diseases. However, the role of IL‐37 in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The aim of this study was to assess the associations between serum levels of IL‐37 and disease activity, inflammatory cytokines, and bone loss in patients with RA. Serum cytokines levels were examined by Enzyme‐linked immunosorbent assay (ELISA). Radiographic bone erosion was assessed using the van der Heijde‐modified Sharp score and bone mineral density (BMD) was measured using DXA. Serum IL‐37 levels in RA patients were significantly higher than those in HCs (p < 0.001), and were significantly positively correlated with clinical parameters of disease activity and serum levels of IL‐17 and IL‐23. In addition, serum IL‐37 levels were significantly higher in patients with stage IV of radiographic bone erosion than those with stage III and stage I–II, and they were significantly higher in those with osteopenia and osteoporosis than in those with normal BMD. Our results suggest that serum IL‐37 levels were increased in patients with RA and were positively associated with disease activity, IL‐17/IL‐23 and bone loss in RA, suggesting that IL‐37 may play a critical role in the pathogenesis of RA.     

High levels of inflammatory cytokines are associated with poor clinical response to steroid treatment and recurrent episodes of type 1 reactions in leprosy

Levels of leprosy antigen-induced interferon-gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in 96 leprosy patients with type 1 reactions (T1R) before, during and after a standard 12-week course of steroids. Peripheral blood mononuclear cells (PBMC) from leprosy patients with untreated T1R produced significantly more TNF-alpha than leprosy patients without T1R. Median levels of IFN-gamma and TNF-alpha in T1R patients fell during treatment with steroids; however, TNF-alpha levels increased as the steroid dose was reduced. Median IL-10 levels increased throughout the steroid treatment period and were associated strongly with TNF-alpha levels. Patients with high cytokine levels had a poorer recovery of sensory or voluntary muscle nerve function, a higher risk of reactivation of symptoms during steroid treatment, and a higher risk of another episode of T1R within 2 months of completing the steroid regimen. Rapid and effective reversal of the inflammatory process in T1R is critical to prevent permanent nerve damage from T1R and monitoring cytokine levels during treatment may be useful.     

Lower respiratory tract infections in early life are associated with obstructive sleep apnea diagnosis during childhood in a large birth cohort

Study ObjectivesSeveral birth cohorts have defined the pivotal role of early lower respiratory tract infections (LRTI) in the inception of pediatric respiratory conditions. However, the association between early LRTI and the development of obstructive sleep apnea (OSA) in children has not been established.MethodsTo investigate whether early LRTIs increase the risk of pediatric OSA, we analyzed clinical data in children followed during the first 5 years in the Boston Birth Cohort (n = 3114). Kaplan–Meier survival estimates and Cox proportional hazards models adjusted by pertinent covariates were used to evaluate the risk of OSA by the age of 5 years between children with LRTI during the first 2 years of life in comparison to those without LRTI during this period.ResultsEarly life LRTI increased the risk of pediatric OSA independently of other pertinent covariates and risk factors (hazard ratio, 1.53; 95% CI, 1.15 to 2.05). Importantly, the association between LRTI and pediatric OSA was limited to LRTIs occurring during the first 2 years of life. Complementarily to this finding, we observed that children who had severe respiratory syncytial virus bronchiolitis during infancy had two times higher odds of OSA at 5 years in comparison with children without this exposure (odds ratio, 2.09; 95% CI, 1.12 to 3.88).ConclusionsChildren with severe LRTIs in early life have significantly increased risk of developing OSA during the first 5 years of life. Our results offer a new paradigm for investigating novel mechanisms and interventions targeting the early pathogenesis of OSA in the pediatric population.     

Newly identified respiratory viruses associated with acute lower respiratory tract infections in children in Lanzou,China, from 2006 to 2009

Nasopharyngeal aspirates were collected from 813 children <14 years old with acute lower respiratory tract infections in Lanzhou, China, from December 2006 to November 2009. PCR or RT-PCR was used to screen for the presence of 10 respiratory viruses. Viral agents were identified in 73.92% (601/813) of specimens, including RSV in 40.71%, hMPV in 6.15%, IFVA in 7.13%, IFVB in 0.98%, PIV1-3 in 7.87%, HCoV-HKU1 in 2.21%, HCoV-NL63 in 3.81%, HRV in 19.93%, AdV in 7.50% and HBoV in 11.56%. Two or more viruses were detected in 34.44% (280/813) of cases. The newly identified respiratory viruses, HBoV, hMPV, HCoV-HKU1 and HCoV-NL63, accounted for 22.01% of the detected viral pathogens. RSV and HRV were frequently detected in patients with bronchiolitis, and hMPV was frequently associated with pneumonia. HCoV-NL63 was found to be one of the causative agents of acute respiratory wheezing in young children. No seasonal variation was found in the incidence of detection of HCoV-HKU1, HCoV-NL63 or HBoV. This 3-year study demonstrated that viral pathogens play an important role in children with ALRTIs, and more attention should be paid to these newly identified viral agents.     

Analysis of the expression of HLA class I, proinflammatory cytokines and chemokines in primary tumors from patients with localized and metastatic renal cell carcinoma

Changes in the human leukocyte antigen (HLA) class I expression and cytokine and chemokine production both by cancer cells and by normal surrounding tissue are believed to be responsible for immune escape and tumor progression. In this study, we compared the tumor expression levels of HLA heavy chain (HLAhc), beta-2-microglobulin (beta2m), chemokines (Interferon-gamma-inducible Protein-10 (IP-10), Interferon-inducible T-cell Alpha-Chemoattractant (I-TAC), Stromal cell-Derived Factor-1 (SDF-1), Macrophage Inflammatory Protein-1-alpha (MIP-1-alpha) and Regulated upon Activation, Normally T-Expressed, and presumably Secreted (RANTES)) and cytokines (Vascular Endothelial Growth Factor (VEGF), Interferon-gamma (IFN-gamma), Interleukin-10 (IL-10), Tumor Growth Factor-beta (TGB-beta)) in primary tumors and adjacent normal tissues from patients with localized and metastatic renal cell carcinoma (RCC) using a quantitative real-time polymerase chain reaction technique. We report that the expression of HLAhc, beta2m and the studied cytokines and chemokines (except for SDF-1) was significantly higher in the tumor (29 samples) than in the normal tissue (14 samples). When we compared the tumor expression levels between patients with localized RCC and patients with advanced metastatic stage, we found that the messenger RNA expression levels of HLAhc and beta2m were much lower in patients with metastatic RCC (6 cases) than in patients with localized cancer (23 cases), with levels similar to those in normal tissue. This was also confirmed on a protein level by immunohistological labeling of tumor tissues. Thirty-nine percent of the analyzed RCC tumors showed partial loss of HLA class I molecules, while 6% of the tumors showed HLA class I total loss. The expression of IP-10, SDF-1 and VEGF-c was also significantly lower in patients with advanced tumor, while the IFN-gamma expression in metastatic RCC was not detectable. Our findings show that primary RCC tumors are characterized by a high expression of HLAhc and a presence of proinflammatory mediators and chemokines. We also observed that disease progression and development of metastasis in RCC are associated with decreased expression of HLAhc, beta2m, IP-10, SDF-1 and IFN-gamma. This microenvironment may suppress the cytotoxic response, creating conditions that favor tumor escape and cancer progression.