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Hormonal and barrier contraception and risk of upper genital tract disease in the PID Evaluation and Clinical Health (PEACH) study.

OBJECTIVE: Among women diagnosed with pelvic inflammatory disease, we examined the associations between hormonal or barrier methods of contraception and upper genital tract infection or inflammation. METHODS: Participants were 563 patients from a treatment trial for pelvic inflammatory disease. All had pelvic pain; pelvic organ tenderness; and leukorrhea, mucopurulent cervicitis, or untreated cervicitis. Contraceptive use within the prior 4 weeks was compared among women with baseline upper genital tract gonorrhea or chlamydia, women with endometritis without upper genital tract gonorrhea or chlamydia, and women with neither upper genital tract gonorrhea or chlamydia nor endometritis. RESULTS: Inconsistent condom use was significantly and independently associated with a 2 to 3 times elevated risk for upper genital tract infection. Upper genital tract gonorrhea or chlamydia was not significantly associated with use of oral contraceptives, use of medroxyprogesterone, condoms used consistently, nor other barrier methods. CONCLUSION: No hormonal or barrier contraceptive method was related to a reduction in upper genital tract disease among women with clinical pelvic inflammatory diseases.

Adolescent↗

The etiology and management of genital ulcers in the Dominican Republic and Peru.

BACKGROUND: Clinical diagnosis of genital ulcers is difficult, and diagnostic tests are least available in settings where rates of disease are highest. The World Health Organization (WHO) has developed protocols for the syndromic management of genital ulcers in resource-poor settings. However, because risk factors, patterns and causes of disease, and antimicrobial susceptibilities differ from region to region and over time, they must be adapted to local situations. GOAL: The goal of this study was to determine etiologic factors, evaluate syndromic management, and compare polymerase chain reaction (PCR) testing with other diagnostic alternatives for genital ulcers among patients attending sexually transmitted disease clinics in the Dominican Republic and Peru. STUDY DESIGN: Eighty-one men with genital ulcers in the Dominican Republic and 63 in Peru underwent identical interviews and identical multiplex PCR (M-PCR) tests of genital lesion specimens for etiologic diagnoses. Algorithms for managing genital ulcers were developed. RESULTS: In the Dominican Republic, 5% were M-PCR-positive for, 26% for, and 43% for herpes simplex virus (HSV); in Peru, 10%, 5%, and 43%, respectively, were positive. The WHO algorithm for treating syphilis and chancroid had a sensitivity of 100%, a positive predictive value (PPV) of 24%, and an overtreatment rate of 76%. A modified algorithm for treating only those without vesicular lesions had 88% sensitivity and a 27% PPV, and the overtreatment rate was reduced to 58%. CONCLUSION: HSV caused 43% of genital ulcers in these populations. The modified algorithm had lower sensitivity but a reduced overtreatment rate. M-PCR testing was more sensitive than standard tests and more specific and sensitive than clinical diagnosis.

Adolescent↗

Interaction of Chlamydia trachomatis with human genital epithelium in culture.

Primary cultures of human endometrial and ectocervical epithelial cells were examined as a new model system to study genital infection by Chlamydia trachomatis. Initial studies demonstrated that these cells were indeed susceptible to chlamydial infection. Inocula, adjusted to produce inclusions in 50 to 80% of equivalent numbers of standard McCoy cells, resulted in infection rates of approximately 15 to 30% for the columnar cells of the endometrium and 5 to 10% for the squamous cells of the ectocervix. Exposure of cultures to DEAE-dextran and centrifugation-assisted inoculation, manipulations reported to enhance infection of HeLa and McCoy cells, did not alter the number of inclusion-positive genital cells. Addition of cycloheximide to the post-inoculation culture medium slightly increased numbers of inclusion-bearing cells while growth of genital cells in hormone-supplemented medium resulted in a variable effect on inclusion development and a significant reduction in the association of radiolabelled organisms with these cells. The basis for the different levels of infection in McCoy versus genital cell cultures was revealed by immunofluorescence analysis of chlamydial association with host cells immediately after inoculation. Chlamydiae failed to adhere to many cells in the genital cell cultures while adherence to McCoy cells was uniform. In addition, the association of radiolabelled C. trachomatis was significantly lower with genital cells than with McCoy cells. Finally, culture conditions were defined which markedly inhibited inclusion development without an immediate loss of chlamydial growth potential. This investigation indicates that primary genital cell cultures are susceptible to chlamydial infection and will be valuable for studies on the nature of C. trachomatis interactions with natural human target cells.

Cells, Cultured↗

Risk factors associated with genital warts in HIV-positive Brazilian women.

AIMS AND BACKGROUND: In Brazil, the female population has been increasingly infected with human immunodeficiency virus (HIV), and uterine cervix carcinoma now represents the second highest cause of mortality. Although HIV infection among women is associated with an increased prevalence of cervical cancer precursors, the co-infection with human papillomavirus (HPV) is considered to be a necessary but not sufficient factor to induce genital lesions. This study was conducted to identify risk factors associated with the history of genital warts among HIV-positive women. METHODS: A comparative cross-sectional evaluation was applied to 141 HIV-positive women. All patients were submitted to colposcopy, smear cytology, directed biopsy, and HPV-DNA detection. The chi-square, Fisher's exact test, and the odds ratio (OR, 95%; confidence interval, CI) were used to evaluate associations between history of genital warts and risk factors. RESULTS: A history of genital warts presented associations with: a) age at first sexual intercourse < or = 17 years (OR, 0.42; CI, 0.16-1.11); b) history of genital warts in sex partners (OR, 11.39; CI, 4.21-30.76), especially with recurrent episodes (OR, 6.60; CI, 2.69-16.12); c) drug addiction (OR, 2.38; CI, 1.09-5.19), especially in crack users (OR, 5.34; CI, 1.64-17.41); d) cervical HPV infection (OR, 2.75; CI 1.09-6.90); e) cervical infection caused by only one HPV type (OR, 2.77; CI 1.06-7.20); f) perianal HPV infection (OR, 2.30; CI, 0.70-7.56), associated with negative results for undetermined risk HPV (OR, 8.41; P = 0.04); and g) no antiretroviral therapy (OR, 3.41; P = 0.07). CONCLUSIONS: Evaluation of behavioral risk factors associated with a genital wart history is an important tool to prevent and reduce persistent HPV infection, and consequently genital cancer precursors in HIV infected women.

Adult↗

A comparison of topical application of penciclovir 1% cream with acyclovir 3% cream for treatment of genital herpes: a randomized, double-blind, multicentre trial.

Genital herpes simplex virus (HSV) infection, a sexually transmitted disease (STD), is the commonest cause of ulcerative genital infections among the young and adult population. The significant association of genital ulceration and transmission of human immunodeficiency virus (HIV) has been shown in many studies. To explore the potential efficacy of topical treatment of genital herpes with penciclovir cream, a randomized, double-blind, multicentre, acyclovir-controlled Phase II clinical trial of penciclovir 1% cream 5 times daily up to 7 days for suppression of genital herpes was conducted in China. A total of 205 patients aged 20-59 years (mean age 36.0+/-8.8 years for acyclovir and 34.8+/-8.4 years for penciclovir) with a clinical diagnosis of genital herpes were randomly allocated to one of the 2 parallel treatment groups and used for analysis. Clinical assessment were made before treatment and followed up at every visit during the study. Our results show that there was an encouraging improvement simultaneously in the 2 groups although no significant differences in clinical efficacy with respect to clinical cure rate, and times to healing, resolution of all symptoms, absence of blisters, cessation of new blisters, crusting, and loss of crust between penciclovir and acyclovir groups in terms of primary, non-primary and total patients were found. However a significantly shorter time to crusting was found in primary penciclovir group when compared with primary acyclovir group. Adverse experience was generally infrequent and mild, and was comparable in the 2 treatment groups. Based on these preliminary clinical findings, further evaluation of penciclovir 3% cream for topical treatment of genital herpes is planned.

Acyclovir↗

[Defenses of the female genital tract against infection].

The female genital tract possesses various systems of defenses against the infectious risk, which appear complementary, additive and even synergistic. These defenses comprise first non immune strategies, passive (synthesis of protective mucus; pH; epithelial barrier) or active (inflammatory reaction; secretion of humoral soluble factors such as lactoferrin), which are likely very efficient to limit the infectious inoculum. Pre-immune defense strategies, both humoral and cellular, yet not well understood, are also possibly involved in rapid protection pre-existing before antigenic stimulation. When these initial lines of defenses have failed, a third strategy, acquired and specific of the pathogen, occurs progressively. This latter associates humoral immune response, with secretory IgA (S-IgA) and IgM (S-IgM), and locally produced IgG (s-IgG), and cellular immune response. The very high amount of IgG in the female genital secretions, at levels more than 10-fold those of IgA, and originating in part from plasma by transudation, is remarkable for a corporeal fluid, the mucosal secretions being most often characterized by the predominance of immunoglobulins of the IgA isotype. The defenses of the female genital tract are largely under the influence of female hormones (menstrual cycle or pregnancy) and of paracrine production of various cytokines. Note that the genital defenses against infectious agents must not decrease the efficiency of the reproduction; indeed, spermatozoa act as potential exo-antigens for the female genital tract, and the inductive capabilities of the genital immunocompetent tissue have to be limited when the epithelial barrier has not been crossed. Systemic immunity acts in a second step to reinforce or substitute the acquired mucosal immunity of the genital tract.

Antibody Formation↗

Effect of immunosuppression on neonatally diethylstilbestrol-induced genital tract lesion and tumor development in female mice.

Neonatal treatment of female rodents with the synthetic estrogen diethylstilbestrol [(DES) CAS: 56-53-1; alpha, alpha'-diethyl-4,4'-dimethoxystilbene] results in immunodeficiency that persists into adulthood, along with progressive development of genital tract lesions. DES-induced immunosuppression was examined as a possible promoter of genital tract lesion and tumor development in BALB/cCrgl female mice. Secondary suppression of T-cell immunity after neonatal DES treatment failed to increase lesion incidence or to promote genital tract tumor development in 8-month-old mice. Although hyperplastic lesions were present in 70% of the genital tracts from DES-treated mice at 8 months of age, apparently few neoplastic cells are present at this time, since transplantation of genital tracts from these animals into syngeneic hosts did not yield tumors. To reduce the possibility that potential tumors were too immunogenic to survive in the syngeneic hosts, genital tract pieces from 12-month-old DES-treated female mice were transplanted into immunosuppressed hosts; only 1 tumor resulted. The tumor was a mixed adenocarcinoma, squamous cell carcinoma, and sarcoma and was immunogenic. These results suggest that immunosurveillance by T-cells is relatively unimportant in DES-induced genital tract lesion development.

Animals↗

Genital herpes and public health: addressing a global problem.

Genital herpes can be caused by herpes simplex virus 2 (HSV-2) or, less commonly, by herpes simplex virus 1 (HSV-1). With a seroprevalence of antibodies to HSV-2 of 22% in the general population, genital herpes is 1 of the 3 most prevalent sexually transmitted diseases (STDs) in the United States. A central issue in the public health problem of genital herpes is the high proportion of genital HSV infections that are unrecognized by both patients and clinicians. Persons who are HSV-2 seropositive may be symptomatic but nevertheless fail to recognize genital herpes; they serve as reservoirs for transmission. Physicians and patients must be aware of the subclinical presentation of genital herpes and the potential these patients have for transmitting HSV. Serious consequences of HSV infection include neonatal herpes and increased risk of human immunodeficiency virus transmission. Recommendations to physicians for prevention include using type-specific tests for HSV when screening for other STDs and testing for HSV when evaluating patients with genital ulcers. Researchers must evaluate the performance of type-specific tests and strategies to prevent transmission.

Global Health↗

The lack of genital ridge vascularization in the early chick embryo: implications in the migration of the primordial germ cells.

It is known that chick primordial germ cells (PGCs) in early embryonic development migrate via the blood vascular system to colonize the gonadal anlagen. Classically, two factors have been involved in the extravasation of PGCs from the blood stream: chemotactic and mechanical factors. An accurate knowledge of the vascular system of the genital ridge is therefore necessary. However, development of gonadal vascularization in bird embryos has been scarcely studied. Our previous studies have shown that the gonadal arteries develop from the mesonephric arteries. The purpose of this work was to study the implications of the development of the vascular system of the chick genital ridge on PGCs colonization. We selected the Hamburger and Hamilton (H-H) stage 18, since the genital ridge is well developed and PGCs actively extravasate. Forty chick embryos of this stage were processed for scanning electron microscopy of vascular corrosion casts and of critical point-dried specimens as well as light microscopy. Our results are conclusive. We could not find any vessel or capillary network supplying the genital ridge; the dorsal aorta and the primordia of the mesonephric arteries were the closest vessels. However, numerous interendothelial spaces were found in the dorsal aorta at the level of the genital ridge. It is suggested that the interendothelial gaps may be very important in the exchange of substances between the avascular genital ridge and the aortic endothelium at this developmental stage. Two different routes are thought to be involved in PGC migration to the gonadal anlage at this stage: the aortic endothelium and the mesonephric arteries. Whereas mechanical factors may be important for extravasation of PGCs in the mesonephric arteries, no reasons have been found from the morphological point of view to support a slowness of the blood flow in the dorsal aorta at the level of the genital ridge facilitating the extravasation.

Animals↗

The development of the Drosophila genital disc.

The imaginal discs of Drosophila melanogaster, which form the adult epidermal structures, are a good experimental model for studying morphogenesis. The genital disc forms the terminalia, which are the most sexually dimorphic structures of the fly. Both sexes of Drosophila have a single genital disc formed by three primordia. The female genital primordium is derived from 8(th) abdominal segment and is located anteriorly, the anal primordium (10 and 11(th) abdominal segments) is located posteriorly, and the male genital primordium from the 9(th) abdominal segment lies between them. In both sexes, only two of these three primordia develop to form the adult terminalia. The anal primordium develops in both sexes but, depending on the genetic sex, will form either male or female analia. However, only one of the genital primordia develops in each sex, forming either the male or the female genitalia. This depends on the genetic sex of the fly. Therefore, the genital disc is a very good experimental model of how the sex-determination and homeotic genes - which determine cell identity - interact to direct the development of a population of cells into male or female terminalia. It has been proposed that the sexually dimorphic development of the genital disc is the result of an integrated genetic input, made up by the sex-determination gene doublesex and the homeotic gene Abdominal-B. This input acts by modulating the response to Hedgehog, Wingless, and Decapentaplegic morphogenetic signals.

Animals↗

Search for human papillomavirus, herpes simplex virus and c-myc oncogene in human genital tumors.

We tested grade III cervical intra-epithelial neoplasms (CIN III), genital invasive carcinomas and healthy genital tissues for the presence of a number of viral and cellular parameters, considered to be risk factors in genital oncogenesis. The results show that: (I) about 30% of genital tumors had homology to HSV-2 BglII N and/or BamHI E DNA fragments; (2) positivity to HSV-2-specific protein ICP10, encoded by sequences within the HSV-2 BamHI E DNA fragment, was detected in 29/55 neoplastic genital tissues but not in healthy genital tissues or tumors at other sites; (3) HPV-16 DNA was found in about 50% of tumor samples, but none of the positive tissues reacted to HPV capsid protein or to the protein encoded by the HPV-16 E6 ORF; (4) 6/8 tumor samples showing homology to HSV-2 DNA fragments also hybridized to HPV-16 DNA; (5) c-myc amplification was not detected in any of the analyzed samples, but tissues from 4 patients were positive for c-myc expression. None of the considered factors was present in all the analyzed samples; nevertheless, some tissues showed the simultaneous involvement of several parameters, suggesting that a number of risk factors may be involved in different steps of human genital oncogenesis.

Adenocarcinoma↗

Enterovirus RNA shedding in the genital tract of childbearing-aged women living in Central Africa.

Enteroviruses (EVs) (Picornaviridae) in the female genital tract may constitute possible sources of antenatal or perinatal infection. The presence of EV genomes in the acellular part of cervicovaginal lavages of 119 non-pregnant childbearing-aged African women was determined using a semiquantitative RT-PCR and hybridization detection assay. EV-specific cervicovaginal IgA and IgG antibodies were also detected by immunocapture ELISA assays. Of 119 CVS samples tested, only 10 (8%) were positive for the detection of EV RNA, demonstrating an genital shedding of EVs in African woman. EV-RNA positivity was not associated with the HIV serostatus or with the presence of semen traces in female genital secretion. The microwell hybridization assay of EV amplified RT-PCR products indicated the presence of low levels of EV genomes, ranging from 50 to 100 RNA copies per ml of genital fluids. EV-specific cervicovaginal IgA or IgG antibodies were detected only in two hemoglobin-positive cervicovaginal secretions samples from women without genital EVs. The lack of EV specific IgA or IgG antibody secretion by the cervicovaginal mucosa supported the hypothesis of genital shedding of EVs without ongoing viral replication in the female genital tract. In conclusion, the findings demonstrated the presence of EV genomes in nearly 10% of childbearing-aged women living in Central Africa, and provided the basis of possible antenatal or perinatal transmission of EV from mother-to-child.

Adolescent↗

Expression of scatter factor/hepatocyte growth factor is regionally correlated with the initiation of sperm motility in murine male genital tract: is scatter factor/hepatocyte growth factor involved in initiation of sperm motility?

Based upon findings that the scatter factor/hepatocyte growth factor (SF/HGF) has strong mitogenic and motogenic properties, and that the sperm cell acquires its fertilizing capacity and motility in the distal parts of mammalian epididymis, the present study was conducted to investigate the role of SF/HGF in initiation of sperm cell motility. This was investigated by determining the expression of SF/HGF in various regions of the murine male genital tract by scatter and cell tracking assays using MDCK epithelial cells, Western blot procedure, and the immunohistochemical procedure using paraffin sections of various regions of the male genital tract. The findings from all these assays indicate that SF/HGF is differentially expressed in various parts of the male genital tract with slight or no expression in the testes, caput epididymis, and vas deferens, and with the highest expression in cauda and corpus (distal) epididymis followed by expression in the corpus (proximal) epididymis. This region-specific SF/HGF expression pattern coincides with the pattern of acquiring the fertilizing capacity and motility by the sperm cell during its transit through the male genital tract. However, wherever SF/HGF was expressed in the male genital tract, its molecular weight was slightly higher (Mr, 82 kD), compared to the SF/HGF expressed in various other somatic tissues (Mr, 78 kD), indicating that the genital tract SF/HGF may be a different molecular species that shares some immunoreactive epitopes with the somatic cell SF/HGF. Incubation of immotile sperm from caput epididymis with the purified human placental SF/HGF of 78 kD initiated motility in 5-15% of sperm population. These results strongly suggest that the SF/HGF-like activity is expressed in the male genital tract in a region-specific manner, and this activity may have a role in initiation of sperm motility acquired during its transit through the epididymis in mammals.

Animals↗

Management of genital herpes.

Oral acyclovir is the therapy of choice for treatment of first-episode genital herpes, for suppression of frequently recurrent genital herpes, and, in selected patients, for episodic treatment of recurrent genital herpes. Topical acyclovir therapy is relatively or totally ineffective and is therefore discouraged. Indications for intravenous acyclovir therapy of mucocutaneous HSV infections include patients hospitalized with severe first-episode genital herpes and immunocompromised patients who have severe infections or who cannot swallow the oral preparation. The most promising investigational drugs are the oral prodrugs valaciclovir and famciclovir. Famciclovir is licensed in the U.S. for treatment of zoster but not for treatment of mucocutaneous genital herpes. When used for episodic therapy of recurrent genital herpes, both famciclovir and valaciclovir effectively reduce the duration of viral shedding, lesion healing times, and the duration of symptoms. Suppressive therapy with famciclovir has also been shown to be effective in reducing the frequency of episodes in women with frequently recurring genital herpes. Although these drugs can be given less frequently than oral acyclovir, there is yet no clear indication that they are more effective or better tolerated than oral acyclovir.

Antiviral Agents↗

Role of genital sex pheromones in Amblyomma americanum and A. maculatum (Acari: Ixodidae).

Amblyomma americanum and A. maculatum were studied to determine if genital sex pheromones were present, as reported in Dermacentor species. Chemical analysis of methanol extracts of the anterior reproductive tracts (source of the genital sex pheromone) of A. americanum and A. maculatum confirmed the presence of the same fatty acids that act as components of the genital sex pheromone in Dermacentor variabilis and D. andersoni. In both Amblyomma species, removal of the anterior reproductive-tract of fed females eliminated the male copulatory response. For A. americanum, use of anterior reproductive tract extracts made with water, methanol, ether and hexane elicited significant probing and copulatory responses by conspecific males. However, in A. maculatum, use of anterior reproductive-tract extracts made with water, methanol, ether, chloroform:methanol (4:1), hexane and pentane did not restore mating response by males. Treatment with known components of Dermacentor genital sex pheromones elicited weak but significant responses in A. americanum, but did not restore male mating responses in A. maculatum. These results indicate that genital sex pheromones exist in A. americanum and are not restricted to the genus Dermacentor. Characteristics of the Amblyomma genital sex pheromone, however, do differ considerably from those in Dermacentor. No genital sex pheromone was present in A. maculatum.

Animals↗

Expression of immunity to intravaginal herpes simplex virus type 2 infection in the genital tract and associated lymph nodes.

Herpes simplex virus type 2 is a human venereal pathogen which causes lethal neurological illness after intravaginal inoculation into BALB/cJ mice. In the present studies, we demonstrate that intravaginal vaccination with an attenuated strain of this virus, which possesses a partial deletion of the thymidine kinase gene, rapidly induced durable immunity to lethal intravaginal challenge with wild-type virus. Such immunity was characterized by a dramatic hyperplasia of genital lymph nodes and a significant reduction in wild-type virus replication and spread from the genital tract following lethal challenge. Of greater importance, immunity to lethal wild-type virus challenge in the genital tract was transferrable to non-immune mice with genital lymph node cells prepared 1 week after intravaginal vaccination but was not transferrable with serum or cells from other lymphoid organs tested at this time. The adoptive transfer of anti-viral immunity to wild-type challenge was also characterized by a diminution in wild-type virus replication and spread from the genital tract. These results suggest that an important component of cellular immunity to genital pathogens may be antigenic stimulation of genital lymph nodes.

Age Factors↗

Attitudes and behavior of college students relative to oral-genital sexuality.

A survey was conducted to determine college students' attitudes toward and behavior relative to oral-genital sexuality. Information concerning attitude and behavior was elicited through the use of an equal-interval attitude scale and a behavior inventory. Responses from 91 students were analyzed. Results of the study indicated that more favorable attitudes toward oral-genital sexuality were expressed by students who had participated in the specific behavior and by students who had experienced sexual intercourse. Attitude toward receiving oral-genital contact was found to be dependent on church attendance. Men were more likely than women to have received oral-genital contact, and students who had participated in sexual intercourse were more likely to have both administered and received oral-genital contact. Receiving oral-genital contact was dependent on church attendance. Women were more likely than men to require love as a prerequisite for their participation in oral-genital contact.

Adult↗

Laboratory evaluation of acute upper genital tract infection.

OBJECTIVE: To evaluate the diagnostic test characteristics of common tests used to diagnose upper genital tract infection. METHODS: Subjects included women who either met the Centers for Disease Control and Prevention's minimal criteria for acute pelvic inflammatory disease or who had other signs of upper genital tract infection (i.e., atypical pelvic pain, abnormal uterine bleeding, or cervicitis). The subjects were evaluated with a baseline interview, comprehensive laboratory testing, and either an endometrial biopsy or laparoscopy for definitive diagnosis of upper genital tract infection. Patients were considered positive for upper genital tract infection if they had any of the following findings: 1) histologic evidence of acute endometriosis or salpingitis, 2) laparoscopic visualization of purulent exudate in the pelvis without another source, or 3) positive testing for Neisseria gonorrhoeae or Chlamydia trachomatis from the endometrium, fallopian tubes, or pelvis. RESULTS: One hundred twenty women with adequate endometrial samples were evaluated between August 1993 and September 1995. The median age of the study population was 24 years: 38% were white, 52% were smokers, 81% were insured by Medicaid or were uninsured, and 67% were single. Sensitivities for elevated white blood cell count (WBC), erythrocyte sedimentation rate, C-reactive protein, and increased vaginal white blood cells are 57, 70, 71, and 78%, respectively. If any one test is abnormal, the sensitivity is 100% and specificity is 18%. If all four tests are abnormal, sensitivity is 29% and specificity is 95%. CONCLUSION: Testing for increased vaginal white blood cells was found to be the most sensitive laboratory indicator for upper genital tract infection, whereas serum WBC was the most specific. No one diagnostic laboratory test is pathognomonic for upper genital tract infection. Combinations of positive tests can improve diagnostic specificity and positive predictive value, but with a diminution of sensitivity and negative predictive value. Combinations of negative tests can reliably exclude upper genital tract infection.

Acute Disease↗