Novel lateral flow assay for point-of-care detection of Neisseria gonorrhoeae infection in syndromic management settings: a cross-sectional performance evaluation.

BACKGROUND: A rapid and affordable point-of-care test is a priority for Neisseria gonorrhoeae control. WHO and Foundation for Innovative New Diagnostics (FIND) have a target product profile for a non-molecular N gonorrhoeae rapid point-of-care test that requires a clinical sensitivity of greater than 80% and a specificity over 95% to be considered useful in syndromic management; test turnaround time should be 30 min or under, and the test should cost less than US$3. A novel lateral flow assay (LFA) was developed to achieve that profile. METHODS: In this cross-sectional study we evaluated the performance of the novel N gonorrhoeae lateral flow assay (NG-LFA) at the primary health-care level in South Africa. Male patients with urethral discharge syndrome and female patients with vaginal discharge syndrome were recruited from five primary health-care facilities in the Buffalo City Metropolitan Municipality health district of South Africa. First-void urine specimens and nurse-collected vaginal swabs were tested in-facility with the NG-LFA and Xpert CT/NG PCR assay. N gonorrhoeae multi-antigen sequence typing (NG-MAST) was performed on all LFA positive specimens. FINDINGS: Between March 7, and Sept 19, 2022, we enrolled 200 male patients with urethral discharge and 200 female patients with vaginal discharge. The median age of male patients was 24 years (IQR 21-31 years), and the median age of female patients was 25 years (IQR 21-32 years). In addition, 23 male patients and 12 female patients who presented at the facility with a partner notification slip were enrolled of whom one (4%) and five (42%) were symptomatic, respectively. NG-LFA and Xpert results were available for all participants. In urine specimens, NG-LFA sensitivity was 96·1% (Wilson 95% CI 91·2-98·3; 123 LFA-positive among 128 PCR-positive specimens) and 91·7% in vaginal swab specimens (78·2-97·1; 33 LFA-positive among 36 PCR-positive). The specificity was 97·2% in urine specimens (90·4-99·2; 70 LFA-negative among 72 PCR-negative) and 96·3% in vaginal specimens (92·2-98·3; 158 LFA-negative among 164 PCR-negative). In 156 LFA-positive specimens, NG-MAST showed 93 different sequence types. INTERPRETATION: The novel NG-LFA had excellent clinical sensitivity and specificity in symptomatic male and female patients. The test met the optimal requirement for sensitivity and the minimal requirement for specificity specified in the target product profile. NG-LFA could provide an important tool to optimise clinical management and reduce excess antibiotic use in settings without direct access to laboratory testing. FUNDING: Global Antimicrobial Resistance Innovation Fund (GAMRIF) via FIND and National Institutes of Health.

Aetiology of vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa: A systematic review and meta-regression.

BACKGROUND: Syndromic management is widely used to treat symptomatic sexually transmitted infections in settings without aetiologic diagnostics. However, underlying aetiologies and consequent treatment suitability are uncertain without regular assessment. This systematic review estimated the distribution, trends, and determinants of aetiologies for vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa (SSA). METHODS AND FINDINGS: We searched Embase, MEDLINE, Global Health, Web of Science, and grey literature from inception until December 20, 2023, for observational studies reporting aetiologic diagnoses among symptomatic populations in SSA. We adjusted observations for diagnostic test performance, used generalised linear mixed-effects meta-regressions to generate estimates, and critically appraised studies using an adapted Joanna Briggs Institute checklist. Of 4,418 identified records, 206 reports were included from 190 studies in 32 countries conducted between 1969 and 2022. In 2015, estimated primary aetiologies for vaginal discharge were candidiasis (69.4% [95% confidence interval (CI): 44.3% to 86.6%], n = 50), bacterial vaginosis (50.0% [95% CI: 32.3% to 67.8%], n = 39), chlamydia (16.2% [95% CI: 8.6% to 28.5%], n = 50), and trichomoniasis (12.9% [95% CI: 7.7% to 20.7%], n = 80); for urethral discharge were gonorrhoea (77.1% [95% CI: 68.1% to 84.1%], n = 68) and chlamydia (21.9% [95% CI: 15.4% to 30.3%], n = 48); and for genital ulcer were herpes simplex virus type 2 (HSV-2) (48.3% [95% CI: 32.9% to 64.1%], n = 47) and syphilis (9.3% [95% CI: 6.4% to 13.4%], n = 117). Temporal variation was substantial, particularly for genital ulcer where HSV-2 replaced chancroid as the primary cause. Aetiologic distributions for each symptom were largely the same across regions and population strata, despite HIV status and age being significantly associated with several infection diagnoses. Limitations of the review include the absence of studies in 16 of 48 SSA countries, substantial heterogeneity in study observations, and impeded assessment of this variability due to incomplete or inconsistent reporting across studies. CONCLUSIONS: In our study, syndrome aetiologies in SSA aligned with World Health Organization guidelines without strong evidence of geographic or demographic variation, supporting broad guideline applicability. Temporal changes underscore the importance of regular aetiologic re-assessment for effective syndromic management. PROSPERO NUMBER: CRD42022348045.

Prospective Cohort Study of Treatment Outcomes of Vaginal Discharge Syndrome in Women in Windhoek, Namibia.

BACKGROUND: Syndromic treatment is the standard of care for vaginal discharge syndrome (VDS) in resource-constrained settings. However, the outcomes of VDS treatment have not been well documented. This study aimed to determine the incidence, risk factors, and microbial etiology of treatment failure in women with VDS. METHODS: This prospective cohort study of women with VDS was conducted between September 2021 and March 2022 at Katutura Intermediate Hospital in Windhoek, Namibia. Microbiological analyses of sexually transmitted infections (STIs; Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis , Mycoplasma genitalium ), bacterial vaginosis, and vulvovaginal candidiasis (VVC) were performed. Treatment outcomes were assessed at 7 and 30 days after treatment, followed by microbial investigation in case of treatment failure. RESULTS: One hundred nine women were enrolled, and 94 (86%) completed the follow-up. At baseline, 58 of 109 women (53%) were diagnosed with STI, 47 of 109 (43%) with bacterial vaginosis, and 45 of 109 (41%) with VVC. Candida albicans (33 of 45; 73%) was the main pathogen in VVC, with fluconazole resistance detected in 8 of 33 isolates (24%); 10 of 12 (80%) of non- albicans Candida species showed resistance. The incidence of treatment failure was 3.6 per 100 person-years at 7 days and 1.0 per 100 person-years at 30 days of follow-up; 17 of 94 women (18%) had recurrent VDS, and 12 of 94 women (13%) had persistent VDS. Vulvovaginal candidiasis (odds ratio, 4.3; 95% confidence interval, 1.7-11; P = 0.002) at baseline was associated with treatment failure. CONCLUSIONS: Treatment failure after syndromic management of VDS is common in resource-constrained settings. Access to diagnostic testing, including fungal culture and susceptibility testing, is recommended to improve outcomes.

Burden and Trends of Symptomatic Sexually Transmitted Infections in Malawi From 2000 to 2021: Comparative Analysis of Survey and Case Report Data.

BACKGROUND: In settings without etiologic testing for sexually transmitted infections (STIs), programs rely on STI symptom data to inform priorities. To evaluate whether self-reported STI symptoms in household surveys consistently represent the STI burden, we compared symptomatic infection rates between survey self-reporting and health facility case reporting in Malawi. METHODS: We analyzed self-reported symptoms and treatment seeking in the past year among sexually active adults from 4 Malawi Demographic and Health Surveys between 2000 and 2015. Bayesian mixed-effects models were used to estimate temporal trends, spatial variation, and sociodemographic determinants. Survey reporting was compared with health facility syndromic diagnoses between 2014 and 2021. RESULTS: In surveys, 11.0% (95% confidence interval, 10.7%-11.4%) of adults reported STI or STI-related symptoms in the last year, of whom 54.2% (52.8%-55.7%) sought treatment. In facilities, the mean annual symptomatic case diagnosis rate was 3.3%. Survey-reported treatment in the last year was 3.8% (95% credible interval, 2.3%-6.1%) for genital ulcer, 3.8% (2.0%-6.7%) for vaginal discharge, and 2.6% (1.2%-4.7%) for urethral discharge. Mean annual diagnosis rates at facilities were 0.5% for genital ulcer, 2.2% for vaginal discharge, and 2.0% for urethral discharge. Both data sources indicated a higher burden of symptoms among women, individuals older than 25 years, and those in Southern Malawi. CONCLUSIONS: Survey and facility case reports indicated similar spatial and demographic patterns of STI symptom burden and care seeking, but implied large differences in the magnitude and relative burden of symptoms, particularly genital ulcer, which could affect program priorities. Targeted etiologic surveillance would improve interpretation of these data to enable more comprehensive STI surveillance.

Measurement of luteinizing hormone surge in vaginal discharge: a potential biomarker that enables simple, non-invasive prediction of the periovulatory period.

BACKGROUND: Predicting the periovulatory period is very important for conception. Current approaches to predicting the periovulatory period include monitoring of basal body temperature and urine luteinizing hormone (LH) concentration; however, these methods are time-consuming. Here, we examined the potential of using vaginal discharge (VD) as a non-invasive means of sample collection for determining the LH surge that indicates ovulation. METHODS: Urine and VD samples were collected from 35 healthy women aged 20-39 years. VD samples were collected with panty liners to reduce the burden on participants. Daily first urine samples and used panty liners were collected from the 10th through 19th days of the menstrual cycle. Urine and VD LH (uLH and vLH) levels in the samples were measured by enzyme-linked immunosorbent assay. Measured vLH baseline and first surge values were analyzed using Student's t-test and ROC curves. RESULTS: Samples for a total of 55 menstrual cycles were collected. We used uLH surge to establish the date of ovulation. uLH surges were observed in 49 cycles, 34 of which had corresponding VD samples that qualified for measurement. Five cycles were excluded due to a lack of vLH data. In the remaining 29 cycles, the vLH surge appeared within the fertile window 90% of the time, and the sensitivity and specificity of the test were 86% and 83%, respectively. CONCLUSIONS: VD has potential for use as a sample for predicting the periovulatory period by measuring LH content.

Characterization and Genome Analysis of the Delftia lacustris Strain LzhVag01 Isolated from Vaginal Discharge.

Delftia has been separated from freshwater, sludge, and soil and has emerged as a novel opportunistic pathogen in the female vagina. However, the genomic characteristics, pathogenicity, and biotechnological properties still need to be comprehensively investigated. In this study, a Delftia strain was isolated from the vaginal discharge of a 43-year-old female with histologically confirmed cervical intraepithelial neoplasm (CIN III), followed by whole-genome sequencing. Phylogenetic analysis and average nucleotide identity (ANI) analysis demonstrated that it belongs to Delftia lacustris, named D. lacustris strain LzhVag01. LzhVag01 was sensitive to ß-lactams, macrolides, and tetracyclines but exhibited resistance to lincoamines, nitroimidazoles, aminoglycosides, and fluoroquinolones. Its genome is a single, circular chromosome of 6,740,460 bp with an average GC content of 66.59%. Whole-genome analysis identified 16 antibiotic resistance-related genes, which match the antimicrobial susceptibility profile of this strain, and 11 potential virulence genes. These pathogenic factors may contribute to its colonization in the vaginal environment and its adaptation and accelerate the progression of cervical cancer. This study sequenced and characterized the whole-genome of Delftia lacustris isolated from vaginal discharge, which provides investigators and clinicians with valuable insights into this uncommon species.

Evaluating differences in milk production, reproductive performance, and survival associated with vaginal discharge characteristics and fever in postpartum dairy cows.

The objective was to assess differences in productive and reproductive performance, and survival associated with vaginal discharge characteristics and fever in postpartum dairy cows located in western and southern states of the United States. This retrospective cohort study included data from 3 experiments conducted in 9 dairies. Vaginal discharge was evaluated twice within 12 DIM and scored on a 5-point scale. The highest vaginal discharge score observed for each cow was used to allocate them into 1 of 5 possible groups (VD group) as follows: VD 1 and 2 (VD 1/2; n = 1,174) = clear mucus or lochia with or without flecks of pus; VD 3 (n = 1,802) = mucopurulent with <50% pus; VD 4 (n = 1,643) = mucopurulent with ≥50% of pus or nonfetid reddish-brownish mucus, n = 1,643; VD 5 = fetid, watery, and reddish-brownish, n = 1,800. All VD 5 cows received treatment according to each herd's protocol. Rectal temperature was assessed in a subset of VD 5 cows, and subsequently divided into fever (rectal temperature ≥39.5°C; n = 334) and no fever (n = 558) groups. A smaller proportion of cows with VD 5 (67.6%) resumed ovarian cyclicity compared with VD 1/2 (76.2%) and VD 4 (72.9%) cows; however, a similar proportion of VD 5 and VD 3 (72.6%) cows resumed ovarian cyclicity. A smaller proportion of VD 5 (85.8%) cows received at least one AI compared with VD 1/2 (91.5%), VD 3 (91.0%), or VD 4 (91.6%) cows. Although we did not detect differences in pregnancy at first AI according to VD, fewer cows with VD 5 (64.4%) were pregnant at 300 DIM than cows with VD 1/2 (76.5%), VD 3 (76.2%), or VD 4 (74.7%). Hazard of pregnancy by 300 DIM was smaller for VD 5 compared with VD 1/2, VD 3, or VD 4 cows. A greater proportion of VD 5 cows were removed from the herd within 300 DIM compared with other VD groups. Milk production was 760 kg lower within 300 DIM for VD 5 compared with VD 2, VD 3, and VD 4, whereas VD 2, VD 3, and VD 4 had similar milk production. We did not detect an association between fever at diagnosis of VD 5 and reproductive performance or milk production. A greater proportion of VD 5 cows without fever were removed from the herd by 300 DIM compared with VD 5 cows with fever. Differences in productive and reproductive performance, and removal of the herd were restricted to fetid, watery, and reddish-brownish vaginal discharge, which was independent of fever.

Effect of rumen-protected choline on dairy cow metabolism, immunity, lactation performance, and vaginal discharge microbiome.

Rumen-protected choline (RPC) promotes benefits in milk production, immunity, and health in dairy cows by optimizing lipid metabolism during transition period management and early lactation. However, the RPC success in dairy cows depends on choline bioavailability, which is affected by the type of protection used in rumen-protected choline. Therefore, our objectives were to determine the effects of a novel RPC on dry matter intake (DMI), identify markers of metabolism and immunity, and evaluate lactation performance. Dry Holstein (n = 48) cows at 245 ± 3 d of gestation were blocked by parity and assigned to control or RPC treatment within each block. Cows enrolled in the RPC treatment received 15 g/d of CholiGEM (Kemin Industries, Cavriago RE, Italy) from 21 d prepartum and 30 g/d of CholiGEM from calving to 21 d postpartum. During the transition period, DMI was measured daily, and blood was sampled weekly for energy-related metabolites such as ß-hydroxybutyrate (BHB), glucose, and nonesterified fatty acids (NEFA), as well as immune function markers such as haptoglobin (Hp) and lipopolysaccharide-binding protein (LPB). Vaginal discharge samples were collected at the calving and 7 d postpartum and stored in microcentrifuge tubes at -80°C until 16S rRNA sequencing. The main responses of body condition score, body weight, DMI, milk yield, milk components, and immune function markers were analyzed using the GLIMMIX procedure of SAS with the effects of treatment, time, parity, and relevant covariates added to the models. The relative abundance of microbiome α-diversity was evaluated by 3 indexes (Chao1, Shannon, and Simpson) and ß-diversity by principal coordinate analysis and permutational multivariate ANOVA. We found no differences in DMI in the pre- and postpartum periods. Cows fed RPC increased the yields of energy- and 3.5% fat-corrected milk and fat yield in primiparous and multiparous cows, with an interaction between treatment and parity for these lactation variables. However, we found no differences in milk protein and lactose up to 150 DIM between treatments. Glucose, NEFA, and BHB had no differences between the treatments. However, RPC decreased BHB numerically (control = 1.07 ± 0.13 vs. RPC = 0.63 ± 0.13) in multiparous on the third week postpartum and tended to reduce the incidence of subclinical ketosis (12.7% vs. 4.2%). No effects for Hp and LPB were found in cows fed RPC. Chao1, Shannon, and Simpson indexes were lower at calving in the RPC treatment than in the Control. However, no differences were found 7 d later for Chao1, Shannon, and Simpson indexes. The vaginal discharge microbiome was altered in cows fed RPC at 7 d postpartum. Fusobacterium, a common pathogen associated with metritis, was reduced in cows fed RPC. Rumen-protected choline enhanced lactation performance and health and altered the vaginal discharge microbiome which is a potential proxy for uterine healthy in dairy cows. The current study's findings corroborate that RPC is a tool to support adaptation to lactation and shed light on opportunities for further research in reproductive health.

Supplementation of rumen-protected lysine during the close-up period improves vaginal discharge clearance in Holstein dairy cows.

We aimed to evaluate the effects of rumen-protected lysine (RPL) supplementation during the close-up period on uterine involution and the resumption of ovarian function in dairy cows. Fifty-two multiparous Holstein cows were categorized based on parity and expected calving date and randomly assigned to the RPL or control (CON) groups. The RPL group received 80 g of RPL daily from day 21 before the expected calving date until parturition. Blood samples were obtained twice weekly from pre-supplementation to 6 weeks postpartum. The onset of luteal activity postpartum was determined via ultrasonography twice weekly for up to 6 weeks postpartum. Uterine involution was tracked at 3 and 5 weeks postpartum through the vaginal discharge score, percentage of polymorphonuclear cells (PMN) in endometrial cytology samples, presence of intrauterine fluid, and gravid horn diameter via ultrasonography. Before supplementation, the RPL group showed amino acid imbalance, which was improved by RPL supplementation. There were no significant differences in the onset of luteal activity, percentage of PMN, intrauterine fluid, or the diameter of the uterine horn between the two groups. The vaginal discharge score in the RPL group decreased from 3 to 5 weeks postpartum, whereas that in the CON groups did not decrease. The number of cows with clinical endometritis was lower in the RPL group. Overall, RPL supplementation during the close-up period enhanced vaginal discharge clearance, potentially averting clinical endometritis, but did not affect the first ovulation in dairy cows.

The advantages of inhouse testing to manage vaginitis treatment.

ABSTRACT: Vaginal discharge is a common presenting complaint in ambulatory care medicine, emergency medicine, primary care, and gynecology, accounting for nearly 10 million office visits annually in the United States. This article discusses management of abnormal vaginal discharge among women of childbearing age and the clinical significance of inhouse diagnostic tools. Provider-performed microscopy is an invaluable clinical skill that allows for immediate diagnosis, treatment, and management of infections and coinfections and should be strongly considered when evaluating a patient.

PECULIARITIES OF THE ORGANS OF THE REPRODUCTIVE SYSTEM OF WOMEN OF REPRODUCTIVE AGE WITH LIVER DYSFUNCTION UNDER THE INFLUENCE OF EXOGENOUS POLLUTANTS.

The widespread use of chemicals by modern society and the prevalence of harmful habits (alcoholism, tobacco smoking, drug addiction) leads to an unnaturally high intake of exogenous pollutants in the human body, which can cause damage to internal organs, including the reproductive system. The aim of this study was to determine the peculiarities of the reproductive system of women of reproductive age with liver dysfunction under the influence of exogenous pollutants, namely, due to harmful working conditions and tobacco smoking. Estimation of activity of liver enzymes was determined by the level of activity of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamate transaminase. The first group (control group) included women with no changes in liver enzyme activity and no history of harmful working conditions or bad habits. The second group (comparison group) - women with no history of harmful working conditions and bad habits, but with laboratory data showing changes in liver enzyme activity. The third group included women who have been working with harmful substances for more than 10 years. The fourth group included women who have smoked for more than 10 years. Changes in objective indicators of women's reproductive system have been studied (vaginal discharge, elasticity of the vaginal wall, epithelial integrity, mucous membranes moistness, pH of the vaginal contents, cytological type, vaginal contents) for all groups. Gynecologic examination and evaluation revealed changes indicating the presence of candidiasis and bacterial vaginosis (caused by anaerobic microbiota) in women who worked in harmful working conditions and smoked, both with and without signs of inflammation. During the objective examination, changes in vaginal discharge were observed in women. Only in 20% of women with smoking habits and 10% of women with harmful working conditions there was no vaginal discharge, while in the control group, such women were the majority. In the group with signs of impaired liver function, the absence of discharge was observed in 30% of women. According to the results of cytological studies, a quarter of women who smoked and one in five women who worked in hazardous conditions had estrogen deficiency, apparently as a result of dysregulation disorders under the influence of pollutants. The inflammatory or cytolytic type of smear, which is a consequence of restructuring, was observed in most women from the smoking group. Also, in the two study groups, there was an increase in the number of cases of fungal or Gardnerella vaginal lesions. Disorders of the genital organs in women under the influence of exogenous pollutants are associated with hepatic and endocrine disorders. Obviously, the mechanisms of formation of the pathological condition cause these disorders, and since women working in harmful conditions and smoking have more developed gynecological manifestations, they have more developed symptoms. Inflammatory changes have been revealed in the cervix for up to 30% of women with the influence of xenobiotics. The relationship between the activity of liver enzymes and epithelial integrity has been revealed as the most significant correlation in study parameters (r=0.71 for alanine aminotransferase and epithelial integrity).

Infective Vaginal Discharge among Women of the Reproductive Age in the Outpatient Department of a Primary Care Centre.

Introduction: Infective vaginal discharge is the most common complaint of the women of reproductive age group attending gynaecology outpatient department. Vaginal discharge may be normal or abnormal. Infective vaginal discharge is usually related to one of the three conditions, like bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis. This study aimed to find out the prevalence of infective vaginal discharge among women of the reproductive age in the outpatient department of a primary care centre. Methods: A descriptive cross-sectional study was carried out among women of the reproductive age group visiting the outpatient Department of the primary care hospital from 1 March 2022 to 1 August 2022 after obtaining ethical approval from the Institutional Review Committee. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 138 patients, infective vaginal discharge was found in 42 (30.43%) (21.32-39.54, 95% Confidence Interval). Bacterial vaginosis was seen in 22 (52.38%), Candida was seen in 13 (30.95%), and Trichomonas was seen in 7 (16.66%) cases. Conclusions: The prevalence of infective vaginal discharge was lower as compared to other studies done in similar settings. Keywords: bacterial; candidiasis; prevalence; vaginitis.

Utility, acceptability and applicability of a nucleic acid amplification test in comparison with a syndromic approach in the management of sexually transmitted diseases at Mulago National Referral Hospital in Uganda (ASTRHA): protocol for an open-label, randomised controlled trial.

INTRODUCTION: Sexually transmitted diseases (STDs) are a major cause of long-term disability. Urethral discharge syndrome (UDS), abnormal vaginal discharge (AVD) and genital ulcer disease (GUD) are very common in low-income and middle-income countries (LMICs), where, due to lack of resources, these infections are managed according to a syndromic approach. Although microbiological diagnosis using nuclear acid amplification tests (NAAT) is already a standard to prescribe targeted treatments in industrialised countries, no randomised clinical trials have been conducted to evaluate clinical usefulness and acceptability of NAAT in comparison with syndromic approach in LMICs. The results of this study could inform diagnostic guidelines since they may suggest an update of the current recommendation if microbiological diagnosis using NAAT in the management of STD is demonstrated to be both useful and acceptable in an LMIC context. METHODS AND ANALYSIS: The primary objective of this randomised, open-label trial is to evaluate the clinical usefulness of a NAAT and its acceptability in comparison with a clinical syndromic approach and to explore whether this test could replace the syndromic approach in the management of STDs at a national referral hospital in Uganda. 220 patients presenting to the STD clinic at Mulago Hospital in Kampala, Uganda with AVD, UDS or GUD will be randomised to either standard of care (syndromic management) or NAAT-based treatment with a 1:1 ratio. All the patients will be asked to return after 2 or 3 weeks for a control visit. Primary outcome will be therapeutic appropriateness. ETHICS AND DISSEMINATION: This trial was approved by the Mulago Hospital Research and Ethical Committee (MHREC2023-97) and the Uganda National Council for Science and Technology (HS31000ES). Patients will give informed consent to participate before taking part in the study. Results will be published in peer-reviewed journals in open-access formats and data made available in anonymised form. TRIAL REGISTRATION NUMBER: NCT05994495.

Intravaginal Foreign Body: A Rare Cause of Persistent Vaginal Discharge in a Child.

ABSTRACT: Vaginal discharge is a common gynaecologic complaint in pre-menarchal girls. However, an intravaginal foreign body (FB) must be suspected when it is persistent. We report the case of a referred 4-year-old girl with a 5-month history of persistent foul-smelling vaginal discharge. Clinical examination confirmed purulent vaginal discharge, along with a vaginal granuloma. A hard, intravaginal object was felt through the anterior rectal wall on digital rectal examination. A plain pelvic X-ray revealed a radiopaque object whose intravaginal position was confirmed by ultrasonography. The patient underwent granuloma excision plus FB removal and antibiotic treatment. The 12-month follow-up was unremarkable.

Exploring vaginal discharge scoring to assess clinical metritis severity: Comparison between intrauterine dextrose and systemic antibiotics treatments.

The objectives of this study were to assess: 1) differences in the metabolic status, systemic inflammation, daily milk yield, and daily rumination time between Holstein dairy cows with different vaginal discharge scores (VDS) in the first 7±3 DIM, and 2) effects of intrauterine dextrose infusion on metabolic status, systemic inflammation, daily milk yield and daily rumination time in dairy cows with VDS4 and VDS5. Cows (n=641) from a farm located in central Pennsylvania were screened at 7±3 DIM (study d 0) to assess vaginal discharge scores. Vaginal discharge was scored using a five-point scale (i.e., 1- clear fluid, 2- <50% white purulent fluid, 3- >50% white purulent fluid, 4- red-brownish fluid without fetid smell, and 5- fetid red-brownish watery fluid). Cows with VDS4 and VDS5 were blocked by parity and randomly assigned to one of two treatment groups: 1) CONV (VDS4 n=15; VDS5 n= 23): two injections of ceftiofur (per label; 6.6 mg/Kg) 72 h apart; and 2) DEX (VDS4 n=15; VDS5 n=22): three intrauterine infusions of a 50% dextrose solution (1 L/cow) every 24 h. Cows that presented a VDS 1, 2, and 3 were categorized as normal vaginal discharge animals (NOMVDS; n=35) and were randomly selected and matched by parity to CONV and DEX cows. Daily milk yield and rumination time for the first 150 DIM were collected from on-farm computer records. Blood samples were collected to assess haptoglobin (HP) and ß-hydroxybutyrate (BHB) concentrations at study d 0, d 7, and d 14 relative to enrollment. Subclinical ketosis was defined as having a BHB concentration >1.2 mmol/dL at any of the sampling points. The data were analyzed using the MIXED and GLIMMIX procedures of SAS as a randomized complete block design. When comparing cows with different VDS (i.e., NOMVDS, VDS4, VDS5) separately, cows with VDS5 had the highest concentration of HP at enrollment compared to cows with VDS4 and NOMVDS; however, cows with VDS4 had higher concentrations of HP compared to cows with NOMVDS. Cows with VDS4 or VDS5 had a higher incidence of subclinical ketosis compared to cows with NOMVDS (p=0.005; VDS4= 62.08±9.16%; VDS5=74.44±6.74%; NOMVDS=34.36±8.53%). Similarly, daily milk yield (p<.0001; VDS4=30.17±1.32 kg/d; VDS5=27.40±1.27 kg/d; NOMVDS=35.14±1.35 kg/d) and daily rumination time (p=0.001; VDS4=490.77±19.44 min; VDS5=465±16.67 min; NOMVDS=558.29±18.80 min) was lower for cows with VDS4 and VDS5 compared to cows with NOMVDS at 7±3 days in milk. When analyzing HP concentration between treatment groups in cows with VDS4 (p=0.70), VDS5 (p=0.25), or VDS4 and VDS5 combined (p=0.31), there was no difference in HP concentration by study d 14 between treatment groups. Interestingly, when only cows with VDS4 were considered for treatment, both treatments, DEX and CONV, increased the daily milk yield to the levels of NOMVDS cows by 14 days in milk. On the other hand, when only cows with VDS5 were considered for treatment, cows treated with DEX produced, on average, 4.48 kg/d less milk in the first 150 days in milk compared to cows treated with CONV or cows that had NOMVDS. Similarly, when cows with either VDS4 or VDS5 were considered for treatment, DEX treatment also impaired milk yield. These results suggest that cows with either VDS 4 or 5 have an altered inflammatory status, and decreased milk yield and rumination compared to cows with NOMVDS. Furthermore, DEX treatment may have similar effects on daily milk yield and metabolic status compared to CONV in cows with VDS4, while DEX is not recommended for cows with VDS5.

Clinical characteristics and risk factors for septic shock in patients with pyometra: A retrospective multicenter cohort study.

BACKGROUND: Pyometra is a disease characterized by the collection of pus in the uterus. The clinical characteristics and etiology of pyometra have not been sufficiently described. In this study, we investigated the clinical characteristics, epidemiology, outcomes, and risk factors of septic shock in patients with pyometra. METHODS: Patients with pyometra admitted to one of four university-affiliated hospitals between January 2010 to August 2022 were enrolled. Pyometra cases associated with peripartum infection and surgical site infection were excluded. Clinical characteristics and outcomes of pyometra were described, and pyometra patients with or without septic shock were compared. RESULTS: A total of 192 patients was included. Twenty-eight-day all-cause mortality was 5.0%, and the 1-year recurrence rate was 6.3%. Median patient age was 77.5 years. The two most common symptoms were abdominal pain (49.0%) and vaginal discharge (47.9%). Escherichia coli (40.1%), Klebsiella pneumoniae (16.7%), and Streptococcus spp.(16.0%) were the pathogens most frequently isolated by conventional culture; those isolated from polymerase chain reaction were Mycoplasma hominis (48.0%), and Ureaplasma spp. (32.0%). In multivariable analysis, fever, uterine perforation, and dementia were associated with increased incidence of septic shock, while vaginal discharge was associated with a lower incidence of septic shock. CONCLUSIONS: Our findings suggest that pyometra is a unique gynecological infectious syndrome in post-menopausal individuals. The most common associated pathogens are similar to those involved in urinary tract infections rather than those of sexually transmitted diseases. Decreased cognitive function could delay early diagnosis of pyometra and lead to septic shock and higher mortality.

Postpartum Necrotizing Myositis With Endometrial Prolapse.

BACKGROUND: Postpartum necrotizing myositis is a rare condition, typically presenting as a complication after uterine artery embolization or uterine compression suturing. Uterine ischemia can cause endometrial necrosis and even myometrial necrosis, which can lead to systemic infection. If a systemic infection is not promptly and actively treated, it may pose significant risk. CASE: A 35-year-old patient who had undergone bilateral uterine artery ligation, modified B-Lynch suture, and multiple compression sutures due to refractory postpartum hemorrhage frequently presented to clinic after postpartum discharge due to persistent fever and vaginal discharge. A bag-like prolapse from the vagina measuring 10×5 cm, accompanied by purulent discharge, was noted 78 days postsurgery. Subsequent pelvic magnetic resonance imaging revealed a uterine basal abscess and postpartum necrotizing myositis; an emergency laparoscopic supracervical hysterectomy was performed, with postoperative pathology confirming the diagnosis. After the patient's discharge, she was readmitted for inpatient treatment of a pelvic abscess. CONCLUSIONS: Although rare, postpartum necrotizing myositis should be considered in postpartum patients presenting with fever, abdominal pain, severe infection symptoms, and abnormal vaginal discharge. Culture and sensitivity testing are recommended to direct appropriate antibiotic therapy.

Intracellular presence of Helicobacter pylori antigen and genes within gastric and vaginal Candida.

BACKGROUND: Helicobacter pylori infections are generally acquired during childhood and affect half of the global population, but its transmission route remains unclear. It is reported that H. pylori can be internalized into Candida, but more evidence is needed for the internalization of H. pylori in human gastrointestinal Candida and vaginal Candida. METHODS: Candida was isolated from vaginal discharge and gastric mucosa biopsies. We PCR-amplified and sequenced H. pylori-specific genes from Candida genomic DNA. Using optical and immunofluorescence microscopy, we identified and observed bacteria-like bodies (BLBs) in Candida isolates and subcultures. Intracellular H. pylori antigen were detected by immunofluorescence using Fluorescein isothiocyanate (FITC)-labeled anti-H. pylori IgG antibodies. Urease activity in H. pylori internalized by Candida was detected by inoculating with urea-based Sabouraud dextrose agar, which changed the agar color from yellow to pink, indicating urease activity. RESULTS: A total of 59 vaginal Candida and two gastric Candida strains were isolated from vaginal discharge and gastric mucosa. Twenty-three isolates were positive for H. pylori 16S rDNA, 12 were positive for cagA and 21 were positive for ureA. The BLBs could be observed in Candida cells, which were positive for H. pylori 16S rDNA, and were viable determined by the LIVE/DEAD BacLight Bacterial Viability kit. Fluorescein isothiocyanate (FITC)-conjugated antibodies could be reacted specifically with H. pylori antigen inside Candida cells by immunofluorescence. Finally, H. pylori-positive Candida remained positive for H. pylori 16S rDNA even after ten subcultures. Urease activity of H. pylori internalized by Candida was positive. CONCLUSION: In the form of BLBs, H. pylori can internalize into gastric Candida and even vaginal Candida, which might have great significance in its transmission and pathogenicity.

Vaginitis with purulent vaginal discharge caused by artificial insemination using frozen Histophilus somni-contaminated semen.

In April 2020, two cows in Japan, developed reproductive disorders accompanied by vaginitis with purulent discharge within 3 days of artificial insemination (AI) with the same lot of frozen semen. Histophilus somni was isolated from the vaginal swabs of both cows as well as from the same lot of frozen semen used for the AI. This incident marks the first reported case of H. somni infection in cattle through AI. The major outer membrane protein gene sequences and pulsed-field gel electrophoresis profiles of the isolates were identical. Moreover, we investigated the antimicrobial activity of 12 frozen semen straws against an H. somni isolate using a disk diffusion test. These straws were sourced from five AI centers and included the same lot of semen used for the AI. Although the composition of semen diluents from individual AI centers is not publicly available, both the same lot of frozen semen used in the AI and other lots produced by the same manufacturer showed lower antimicrobial activity than semen from other manufacturers. These results strongly suggest that the two vaginitis were caused by AI using H. somni-contaminated frozen semen because of insufficient antimicrobial activity to inhibit bacterial growth. The minimum inhibitory concentrations of the six antimicrobials recommended for addition to frozen semen in isolates were below the recommended concentrations, suggesting that proper addition could have prevented this incident. This highlights the importance of conducting periodical checks on the antibacterial activity of frozen semen to prevent the transmission of pathogens via AI.

Progesterone-independent endometrial mRNA expression in dairy cows with clinical or subclinical endometritis.

Up to 50 % of dairy cows fail to resolve uterine involution and develop chronic clinical (CE) or subclinical endometritis (SE) 21 days after calving. Clinical endometritis is associated with purulent discharge, while SE is not associated with overt clinical signs. Along with numerous knowledge gaps related to its pathogenesis, SE does not allow for a straightforward and effective therapy. Therefore, it is crucial to unravel differences in the expression of genes among healthy, CE, and SE cows. This might contribute to the discovery of new drug candidates and, in consequence, a potentially effective treatment. In the present study, cows between 21 and 28 days postpartum (PP) were examined using vaginoscopy for the presence of vaginal discharge and endometrial cytology for the determination of the endometrial polymorphonuclear cell (PMN) percentage. Next, an endometrial biopsy sample was taken to investigate the expression of 13 selected candidate genes by qPCR. Uterine health status was assigned to healthy (absence of abnormal vaginal discharge and ≤5 % PMN, n = 13), SE (absence of abnormal vaginal discharge and >5 % PMN, n = 30), and CE (mucopurulent or purulent vaginal discharge and >5 % PMN, n = 9). At the same time, a blood sample was collected to assess serum progesterone concentration and to categorize cows as low (≤1 ng/mL) or high (>1 ng/mL) in progesterone. High expression of IL1B, IL6, IL17A, CXCL8, PTGES, PTGS1, PTGS2, and INHBA genes and low expression of FST was noted in the endometrium of CE compared to healthy cows. Increased endometrial INHBA expression was observed in both SE and CE compared to healthy cows. Interestingly, greater expression of PTGES and PRXL2B genes and lower expression of PTGS2 were characteristic of SE versus CE or healthy. Among cows with no overt clinical symptoms of uterine disease (healthy and SE), the endometrial expression of IL1 B, CXCL8, and PTGES was greater in cows with high versus low serum progesterone. Several genes were differentially expressed among healthy, SE, and CE cows indicating different pathways for the development of different uterine diseases. In conclusion, we found progesterone-independent SE markers, which suggests that low endometrial PTGS2 expression may be indicative of an inadequate immune response and thus contribute to the pathogenesis of SE.