Importancia clínica del aislamiento de Haemophilus spp. (excluyendo H. ducreyi) en muestras genitales. Revisión sistemática / Clinical significance of isolation of Haemophilus no ducreyi in genital samples. Systematic review

Introducción y objetivos Actualmente el diagnóstico microbiológico de las infecciones genitales se realiza con métodos moleculares, los cuales permiten detectar agentes etiológicos menos frecuentes, pero con potencial importancia patogénica, como Haemophilus spp. El objetivo de esta revisión es analizar y resaltar la importancia clínica del aislamiento de Haemophilus spp. en infecciones genitales y rectales, excluyendo H. ducreyi. Material y métodos Se ha realizado una revisión sistemática en base a una búsqueda exhaustiva de las publicaciones incluidas en la base de datos MEDLINE hasta el 5 de agosto de 2021, sobre la presencia de Haemophilus spp. en infecciones genitales y rectales, excluyendo H. ducreyi. Resultados Tras revisar lo descrito en la literatura, las especies de Haemophilus (excluyendo H. ducreyi: HSNOD) se detectaron en 2397 episodios de infección genital, siendo las especies más frecuentemente aisladas H. influenzae y H. parainfluenzae. La mayoría de los episodios (87,6%) están constituidos por aislamiento único. Existe un ligero predominio en mujeres (48,3%) donde puede producir cuadros de vaginitis, salpingitis, endometritis o complicaciones durante el embarazo. En hombres, el cuadro clínico suele corresponder a una uretritis. La mayoría de las muestras corresponde a exudados vaginales y uretrales, con una representación minoritaria a nivel rectal (2,3%). Conclusión HSNOD desempeña un papel patogénico relevante en episodios de infección genital, por lo que los protocolos de diagnóstico microbiológico deben incluir métodos que permitan su detección, así como incluirlos en el espectro etiológico de este tipo de cuadros clínicos (AU)

Introduction and objectives Currently, the microbiological diagnosis of genital infections is carried out with molecular methods, which allow the detection of less frequent etiological agents but with potential pathogenic importance, such as Haemophilus spp. The objective of this review is to analyze and highlight the clinical importance of the isolation of Haemophilus spp. in genital and rectal infections, excluding H. ducreyi. Material and methods A systematic review was carried out based on an exhaustive search of the publications included in the MEDLINE database up to August 5, 2021, on the presence of Haemophilus spp. in genital and rectal infections, excluding H. ducreyi. Results After reviewing what was described in the literature, Haemophilus spp. (excluding H. ducreyi: HSNOD) was detected in 2397 episodes of genital infection, the most frequently isolated species being H. influenzae and H. parainfluenzae. Most of the episodes (87.6%) are constituted by single isolation. There is a slight predominance in women (48.3%) where it can cause vaginitis, salpingitis, endometritis or complications during pregnancy. In men, the clinical picture usually corresponds to urethritis. Most of the samples correspond to vaginal and urethral exudates, with a minority representation at the rectal level (2.3%). Conclusion HSNOD plays a relevant pathogenic role in episodes of genital infection, so microbiological diagnostic protocols must include methods that allow their detection, as well as include them in the etiological spectrum of this type of clinical picture (AU)

Detection of COVID-19 in a Vulvar Lesion.

As new information about coronavirus disease 2019 (COVID-19) is rapidly discovered, clinicians are better equipped to make informed decisions for their patients. While current research suggests COVID-19 viral antigen is not found in vaginal secretions, its detectability in the female lower genital tract may have clinical implications for obstetric and gynecologic care for women. We present a case of a woman at 31 weeks' gestation with simultaneous upper respiratory symptoms and vulvovaginitis. She was found to have a vulvar lesion positive for severe acute respiratory syndrome-COVID by viral swab. This case shows that COVID-19 is detectable in the vulva. This may have implications for health care workers' exposure and personal protective equipment needs. While vertical transmission has largely not been reported, the presence of detectable virus in the female lower genital tract makes this a continued possibility and area of study. KEY POINTS: · COVID-19 is detectable in the female lower genital tract.. · The detection of COVID-19 in the vulva may have implications for personal protective equipment use.. · The detection of COVID-19 in vulvovaginal lesions makes vertical transmission a continued possibility..

Bovine herpesvirus-1 in three major milk sheds of Ethiopia: Serostatus and association with reproductive disorders in dairy cattle.

Bovine herpesvirus-1 (BHV-1) causes infectious bovine rhinotracheitis (IBR), and infectious pustular vulvovaginitis (IPV) in cows and infectious pustular balanopostitis (IPB) in bulls worldwide. Infection of seronegative cattle with BHV-1 leads to abortion, retention of fetal membranes, increased service per conception, metritis and oophoritis. As part of an ongoing study on infectious causes of reproductive disorders in Ethiopia, this investigation aims at assessing the role of BHV-1 in the disorders and the risk factors affecting its seroprevalence. A cross-sectional study was conducted on a total of 1379 randomly selected dairy cattle from 149 herds. These dairy cattle were sampled from milks sheds of central (n = 555), western (n = 195) and southern (n = 629) Ethiopia. Blocking enzyme-linked immunosorbent assay (B-ELISA) was applied to detect antibodies specific to BHV-1. Additionally, a semi-structured questionnaire was administered and farm records were assessed to capture potential risk factors associated with BHV-1 seropositivity. Univariable and multivariable random-effects logistic regression analyses were used to assess potential risk factors associated with BHV-1 serostatus. Model fitness and reliability were assessed using the Hosmer and Lemeshow method and the receiver operating curve (ROC) respectively. An overall herd level BHV-1 seroprevalence of 81.8% (95% confidence interval (CI): 74.7-87.7%) and individual animal level seroprevalence of 41.0% (95% CI: 38.4-43.7%) were found. In a random-effects multivariable logistic regression model, the seroprevalence of BHV-1 exposure was higher in dairy cattle from breeding (Odds ratio [OR] = 1.3; p = 0.036) than in commercial (OR = 0.9; p = 0.137) and small-holder farms. Geographically, the prevalence was higher in western (OR = 1.4; p < 0.001) and southern Ethiopia (OR = 1.2; p < 0.001) than in central regions. BHV-1 seropositive cows had higher (p < 0.05) odds of clinical reproductive disorders including abortion, retained fetal membranes, stillbirth, birth of weak calf and metritis compared to seronegative cows. Thus, it is suggested that BHV-1 should be considered as differential diagnosis among improved dairy cattle herds with reproductive disorders in Ethiopia.

A novel bovine papillomavirus type in the genus Dyokappapapillomavirus.

Papillomaviruses are a diverse group of viruses that are known to infect a wide range of animal species. Bovine papillomaviruses (BPVs) are divided into at least 21 genotypes (BPV1 to BPV21),  with most BPV isolates/strains described to date belonging to one of four genera, including Deltapapillomavirus, Xipapillomavirus, Epsilonpapillomavirus and Dyoxipapillomavirus. Here, we describe the identification and genetic characterization of a new BPV type in the genus Dyokappapapillomavirus. A farm in the state of New York, USA, reported chronic cases of vulvovaginitis in Holstein cows in 2016. Biopsies and/or swab samples collected from the vaginal mucosa were subjected to diagnostic investigation. Conventional diagnostic assays yielded negative results, and vaginal swab samples were subjected to viral metagenomic sequencing. Notably, BLAST searches revealed a papillomavirus genome with 7480 bp in length (67% nt sequence identity to BPV16). Additionally, phylogenetic analysis of the L1 gene of the papillomavirus identified here (tentatively named BPV22) revealed that it clusters with members of the genus Dyokappapapillomavirus. Interestingly, the recently identified BPV16, which was detected in fibropapilloma lesions in cattle also clusters within the Dyokappapapillomavirus group. Each virus, however, forms a separate branch in the phylogenetic tree. These results indicate that the putative BPV22 represents the second BPV within the genus Dyokappapapillomavirus.

Seminal transmission of lumpy skin disease virus in heifers.

It is known that lumpy skin disease virus (LSDV) can be shed in bull semen following infection and also that artificial insemination (AI) poses a biosecurity risk. However, it is not known whether the use of LSDV infected semen in AI poses a biosecurity risk. The aim of this study was to investigate whether LSDV, transmitted through semen, can infect cows and their embryos. Two controlled trials were performed simultaneously. Eleven young beef heifers, naïve to LSDV, were synchronized using an OvSynch protocol and inseminated on Day 0 with fresh semen spiked with a field strain of LSDV on day 0. Six of the heifers were superovulated on Day 1 using pregnant mare serum gonadotropin, and embryos were flushed from these heifers on Day 6. Blood and serum samples were collected from Day 4 until Day 27 to determine the presence of LSDV by PCR and virus isolation, and the presence of antibodies against LSDV by SNT. The first clinical signs of LSD were noticed on Day 10, followed by severe generalized LSD in three heifers and mild LSD in two more heifers. Two heifers were humanely euthanized due to severe unresponsive stranguria. LSDV was detected by PCR, virus isolation or electron microscopy in blood, embryos and organs of experimentally infected animals; and eight heifers had seroconverted by Day 27. Two control animals were not affected. This is the first report of experimental seminal transmission of LSDV in cattle.

Acute cervicitis and vulvovaginitis may be associated with Cytomegalovirus.

Cytomegalovirus (CMV) infection in immunocompetent hosts is generally asymptomatic or may present as a mononucleosic syndrome. Its association with acute cervicitis and vulvovaginitis has rarely been reported. A 24-year-old woman presented with pelvic pain, vulvodynia, abnormal vaginal discharge, burning with urination, fatigue, fever, vomiting and diarrhoea. The vulva and cervix were red with vesicular lesions on the cervix. Genital herpes simplex infection (HSV) was suspected and valacyclovir was given orally. However, serial viral cultures performed 7 weeks apart did not isolate HSV as suspected, but CMV was confirmed by immunofluorescence and early antigen research. Blood tests confirmed an acute CMV infection. Typical inclusions were found at histology. Symptoms resolved slowly with persistence of cervical lesions at 7 weeks from diagnosis. The frequency of CMV genital infection is probably underestimated. The infection is not always asymptomatic and might be confused with genital HSV infection. The clinical course is longer.

[Use of atomic force microscopy to study the cytomorphological signs of papillomavirus infection].

The paper presents the results of studying genital squamous epitheliocytes from human papillomavirus-infected female patients by cytology and atomic force microscopy. The squamous epitheliocytes with and without cytomorphological signs of papillomavirus infection (koilocytosis, dyskeratosis, parakeratosis, hyperkeratosis) have been compared. Examining the surface of the squamous epithelium has yielded quantitative characteristics of infection-induced surface changes.

Granular Vulvovaginitis Syndrome in Nelore pubertal and post pubertal replacement heifers under tropical conditions: role of Mycoplasma spp., Ureaplasma diversum and BHV-1.

In order to determine the role of Mycoplasma spp, Ureaplasma diversum and BHV-1 as causal agents of Granular Vulvovaginitis Syndrome in Nelore heifers raised under tropical conditions and based on the hypothesis that stressful conditions during puberty or breeding season would be a determinant factor for the infection, 340 heifers not vaccinated against BHV-1 were divided in Post-pubertal, in the beginning of the first breeding season, and Pubertal heifers. The vaginal lesion score (VLS) Grade 1 to 4 was giving according to lesion area and severity. Vaginal mucus was used to isolate Mycoplasma spp., Ureaplasma diversum and BHV-1. The predominant VLS was 2. No sample was positive for BHV-1; 48% were positive for Mycoplasma spp., Ureaplasma diversum, or both, with predominance of Ureaplasma diversum. Serum neutralization for BHV-1 showed more positive animals in pubertal group (23%); 3 of the paired sera demonstrated seroconversion. These data indicated that post-pubertal and pubertal Nelore heifers raised under extensive conditions are more susceptible to Mycoplasma spp. and Ureaplasma diversum. The hypothesis that the stress of pubertal period could lead to an acute vaginal infection by HBV-1 was not proofed.

Vaginal heat shock protein expression in symptom-free women with a history of recurrent vulvovaginitis.

OBJECTIVES: The cause of recurrent vulvovaginitis remains unexplained in most cases. Heat shock protein synthesis is induced under conditions of stress; its presence in vaginal samples from women who were between episodes of recurrent vulvovaginitis thus might reflect a persistent perturbation in the local milieu. STUDY DESIGN: We undertook an evaluation by means of enzyme-linked immunosorbent assay of 60-kd heat shock protein and inducible 70-kd heat shock protein expressions in vaginal wash samples from 24 symptom-free women with a history of recurrent vulvovaginitis and 19 matched control subjects. The samples were also tested for Candida albicans, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, and human papillomavirus by polymerase chain reaction; for bacterial vaginosis by clinical and microbiologic evaluation; and for interleukin 10, interleukin 1, interleukin 8, RANTES, and eotaxin by enzyme-linked immunosorbent assay. RESULTS: The presence of 60-kd heat shock protein was detected in 11 women with recurrent vulvovaginitis (45.8%) and 1 control subject (5.3%, P =.005). Similarly, 70-kd heat shock protein was present in 8 patients with recurrent vulvovaginitis (33.3%) and no control subjects (P =.005). The presence of 60-kd heat shock protein and the presence of 70-kd heat shock protein were correlated with each other (P =.02), as were both 60-kd heat shock protein (P =.006) and 70-kd heat shock protein (P =.01) correlated with IL-10. There was no relation between the presence of 60-kd heat shock protein or 70-kd heat shock protein and detection of IL-1, IL-8, or any microorganism. CONCLUSION: The expression of heat shock proteins and IL-10 in the vaginas of women with a history of recurrent vulvovaginitis but not in the vaginas of control subjects suggests the existence of differences in the vaginal milieu between the 2 groups, even when both are without vaginal symptoms.

Herpes simplex virus.

Herpes simplex virus (HSV) infection is prevalent worldwide. Herpes labialis, caused predominantly by HSV-1, and herpes vulvovaginitis, caused predominantly by HSV-2, may result in significant morbidity and mortality for infected neonates exposed during delivery. The diagnosis of HSV infection is made by serological testing, viral culture, or polymerase chain reaction. Women with primary herpes vulvovaginitis exhibit a painful vesicular rash which is self-limited but may be followed by multiple recurrences. Women at greatest risk to transmit HSV to their neonates are those who experience their first episode of HSV during the latter stage of pregnancy. If infected, their neonates may have localized skin, eye and mucosal lesions, invasive central nervous system infection, or disseminated disease. Because of the potentially devastating outcome for a baby infected with HSV, pregnant women with active HSV lesions at delivery should be offered a cesarean section. Still, many neonates who are infected with HSV are born to women with asymptomatic HSV shedding. Therefore, prevention of HSV during pregnancy is exceedingly important.

Mixed vaginal infections of Balb/c mice with low virulent herpes simplex type 1 strains result in restoration of virulence properties: vaginitis/vulvitis and neuroinvasiveness.

Vaginal infections of BALB/c Ann mice with herpes simplex virus type 1 (HSV-1) were studied. Mice were inoculated with virulent strains ANG path and 17 syn+ or low-virulent recombinant strains 27/III and 17-syn3 that differ from parental strains in their glycoprotein B (gB) gene sequences. When low-virulent strains were inoculated separately, no vaginitis/vulvitis was produced despite replication in the vagina. In contrast, after coinfection of mice with the two low-virulent strains, vaginitis/vulvitis was produced and virus could be recovered from the central nervous system (CNS). Two of the CNS isolates produced vaginitis/vulvitis, neuroinvasiveness and death of mice after vaginal infection. Restriction fragment analysis and sequencing were used to assess recombination events in the gB gene sequence of the CNS isolates. After mixed vaginal infection recombination between non-virulent HSV strains occurs, resulting in vaginitis/vulvitis and neuroinvasiveness. No correlation was detected between the syncytial phenotype and local vaginal virulence. Virulence of HSV is not solely dependent on gB function; it seems to be more probable that several genes act in concert to induce virulence and neuroinvasiveness.

Virulence and genotype of a bovine herpesvirus 1 isolate from semen of a subclinically infected bull.

A bovine herpesvirus 1 (BHV-1) isolate from the semen of a subclinically infected bull was administered to cattle by various routes to assess its virulence. Cattle that were artificially inseminated or inoculated intrapreputially did not develop clinical signs, but did transmit the virus to contact cattle. However, the isolate induced severe signs of rhinotracheitis and vulvovaginitis in cattle that were inoculated by the intravaginal, intranasal or intravenous routes, but did not infect the fetus. The isolate was therefore not of low virulence. Analysis with DNA restriction enzymes could not assign the isolate to either the BHV-1.1 or BHV-1.2 genotype.

Vulvar vestibulitis. A histopathologic study of 36 cases, including human papillomavirus in situ hybridization analysis.

Vulvar vestibulitis is a recently described clinical condition of unknown etiology. Human papillomavirus (HPV) infection has been implicated as a causal pathogen by some investigators. Because reports on this entity are few, we studied the pathologic features of vestibulectomy specimens from 36 women with a clinical diagnosis of vulvar vestibulitis. The patients' ages ranged from 19 to 53 years (mean, 31 years). Bilateral excisions were performed in 34 patients and a unilateral excision in two. Minor vestibular glands or ducts were identified in 28 patients (78%). Chronic inflammation was present in all specimens. The inflammatory infiltrate consisted predominantly of T lymphocytes and plasma cells with smaller numbers of B lymphocytes. Lymphoid follicles were present in four patients, ulcers in two. The predominant site of inflammation was the squamous mucosa, especially the lamina propria, where the degree of inflammation was graded as mild in 11 patients, moderate in 21 patients, and severe in four patients. To a lesser degree, the inflammation also typically involved the periglandular/periductal connective tissue of the minor vestibular glands, where it was graded as mild in 25 patients and moderate in three patients. Foci of squamous metaplasia were observed in 27 of 28 patients with demonstrable vestibular ducts or glands. Nodular hyperplasia of a vestibular gland (so-called "adenoma") occurred in one patient. In six selected cases, fungi were not identified on silver stains. Morphologic findings of HPV infection, such as koilocytotic atypia or squamous dysplasia, were absent. In-situ hybridization studies for HPV types 6, 11, 16, 18, 31 and 35 were negative in all 36 cases. We conclude that (a) vestibulectomy specimens from patients with a clinical diagnosis of vulvar vestibulitis typically show a chronic inflammatory cell infiltrate that predominantly involves the mucosal lamina propria and periglandular/periductal connective tissue and (b) a pathogenetic role for HPV types 6, 11, 16, 18, 31 and 35 is not substantiated.