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PubMedDate not supplied

Chlamydia trachomatis infection among pregnant women: prevalence and prenatal importance.

BACKGROUND: Chlamydia trachomatis infection in pregnant women is suspected to result in low birth-weight and premature infants. We conducted studies to ascertain the prevalence of this infection among pregnant women in our setting and whether its presence is a risk factor for low birth-weight or prematurity. METHODS: In the first study, 94 pregnant women between 26 and 30 weeks of gestation were screened for infection with Chlamydia trachomatis. The second investigated a cohort of 172 pregnant women presenting in spontaneous labour. The infection status was related to perinatal outcome in terms of birth-weight and gestation. In both the studies, Chlamydia trachomatis infection was diagnosed using the Chlamydiazyme test performed on endocervical swabs. RESULTS: The prevalence of Chlamydia trachomatis infection in mid-pregnancy and at labour was 17% (16/94) and 18.6% (32/172), respectively. Women with infection were relatively older than those without it [mean (SD) age: 26.6 (4.5) years v. 24.8 (3.6) years, p = 0.01]. The mean (SD) birth-weight [2869 (611) g v. 2814 (496) g], gestation [38.5 (2.6) weeks v. 38.3 (2.0) weeks], and incidence of low birth-weight [18.7% v. 20.7%] as well as prematurity [9.4% v. 10.7%] were similar among neonates born to women with or without infection. Neonates born to infected mothers experienced purulent conjunctivitis more frequently than those born to non-infected mothers [12.5% v. 2.8%, p = 0.04]. CONCLUSION: Chlamydia trachomatis is a relatively common infection in pregnant women. However, it was not associated with either low birth-weight or prematurity.

Adult↗

PubMed1977

Etiology of nongonococcal urethritis. Evidence for Chlamydia trachomatis and Ureaplasma urealyticum.

Chlamydia trachomatis, Ureaplasma urealyticum (T-mycoplasma), and Hemophilus vaginalis have previously been considered possible etiological agents in nongonococcal urethritis (NGU). In this study, current C. trachomatis infection was confirmed by culture and (or) micro-immunofluorescence serology in 26 of 69 men experiencing afirst episode of NGU, and 1 of 39 with no urethritis. Serum IgM immunofluorescent antibody to chlamydia was demonstrated in 16 of 20 men with chlamydia culture positive NGU, and 3 of 39 with chlamydia culture negative NG, and none of 34 with no urethritis. 9 of 10 culture positive men with less than or equal to 10 days symptoms developed immunofluorescent antibody seroconversion in paired sera. U. realyticum was isolated significantly more often and in significantly higher concentration from first voided urine from chlamydia-negative cases of NGU than from chlamydia-positive NGU. Ureaplasmacidal antibody titers increased fourfold in six men, four of whom had negative cultures for for unreaplasma. H. vaginalis was isolated from c9 of 33 men with no urethritis and 2 of 69 with NGU. C. trachomatis is susceptible, and U. urealyticum is resistant to sulfonamides. A 10-day course of sulfisoxazole therapy produced improvement in 13 of 13 chlamydia-positive, unreaplasma-negative, and only 14 of 29 chlamydia-negative, unreaplasma-positive NGU cases (P less than 0.002). Thus, culture, serology, and response to therapy support the etiologic role of chlamydia in NGU. Quantitative culture and response to therapy suggest U. unrealyticum may cause many cases of chlamydia-netative NGU.

Adult↗

PubMed2001

CD8+ T cells recognize an inclusion membrane-associated protein from the vacuolar pathogen Chlamydia trachomatis.

During infection with Chlamydia trachomatis, CD8(+) T cells are primed, even though the bacteria remain confined to a host cell vacuole throughout their developmental cycle. Because CD8(+) T cells recognize antigens processed from cytosolic proteins, the Chlamydia antigens recognized by these CD8(+) T cells very likely have access to the host cell cytoplasm during infection. The identity of these C. trachomatis proteins has remained elusive, even though their localization suggests they may play important roles in the biology of the organism. Here we use a retroviral expression system to identify Cap1, a 31-kDa protein from C. trachomatis recognized by protective CD8(+) T cells. Cap1 contains no strong homology to any known protein. Immunofluorescence microscopy by using Cap1-specific antibody demonstrates that this protein is localized to the vacuolar membrane. Cap1 is virtually identical among the human C. trachomatis serovars, suggesting that a vaccine incorporating Cap1 might enable the vaccine to protect against all C. trachomatis serovars. The identification of proteins such as Cap1 that associate with the inclusion membrane will be required to fully understand the interaction of C. trachomatis with its host cell.

Animals↗

PubMed1982

Quantitative study of Chlamydia trachomatis in genital infection.

Chlamydia trachomatis inclusion counts on inoculated McCoy cell coverslips were used as an index of the degree of infection of the cervix in women and of the urethra in men with urethritis. High inclusion counts were obtained significantly more often from men than from women, from women with cervical ectopy, and from women who had had recent sexual intercourse. Low inclusion counts were significantly more common in men with a past history of gonococcal urethritis. Higher chlamydial isolation rates in women with gonorrhoea and in women taking the contraceptive pill could not be attributed to a greater degree of infection, since inclusion counts were not raised in these patients. There was evidence that strains of C trachomatis might vary in their ability to establish themselves in the genital tract because high counts in men with NGU were associated with high counts in their female consorts and the levels of counts in men were associated with the frequency of chlamydial isolation from their female consorts. The relatively simple technique of inclusion counts in cultures for chlamydia from the genital tract may yield valuable information about the behaviour of different strains of C trachomatis in causing pathological changes, in the transmission of infection between individuals, and in the response to specific chemotherapy.

Adolescent↗

PubMed2006

[DNA sequence polymorphism of Chlamydia trachomatis omp1 gene].

A method for detection and genotyping of genital Chlamydia trachomatis infections based on omp1 gene amplification and sequencing was developed, and the character of omp1 gene of Chlamydia trachomatis was analysed. Urethral or endocervical specimens were collected from 323 patients attending STD clinics in Hengyang, Shanghai, Guangzhou and Jiangmen from November, 2003 to May, 2004. DNA was extracted by usual method, and an approximately 980bp fragment from the major outer membrane protein (omp1) gene of Chlamydia trachomatis was amplified by nested polymerase chain reaction (nPCR). The PCR products were purified by DNA agarose gel purification system and the sequence of the omp1 gene was determined by using an ABI PRISM 3700 Genetic Analyser, and genotyping was performed by BLAST similarity search. Multiple alignment was performed with CLUSTAL package (CLUSTAL X), and a phylogenetic tree was constructed by Mega3 software to illustrate the evolutionary relationships between clinical isolates and reference strains of C. trachomatis obtained from GenBank. All variable sequences were submitted to GenBank by Banklt programe. The overall prevalence of urogenital chlamydial infection was 29.7% (96 of 323). All the 96 C. trachomatis-positive cases were sequenced, and 10 genotypes and 28 genetic variants were detected. The most prevalent genotype was E(34.4%), followed by J(25.0%), D(12.5%), F(8.3%), G(7.3%), H(3.1%), Ba(3.1%), K(3.1%), Da (2.1% ), 1 (1.1%). The distribution of C. trachomatis genotypes in the four cities in sourth China was similar to other countries in the world. The omp1 gene was highly conserved for genotype E and F, but appeared slightly less conserved for other genotypes, where the sequences displayed one or several nucleotide substitutions relatived to the corresponding reference sequence. And a similar recombination was found between genotypes Ba and D in CD1. Phylogenetic tree showed that Chlamydia trachomatis genotypes were mainly divided into three clusters, according to previous grouping in the B, F-G, and C complexes. Clusters F-G and C were characterized by small genetic distances within each cluster, but clusters B displayed larger genetic distances. And the clinical isolates were highly related to the reference strains. It is concluded that the isolated Chlamydia trachomatis strains exhibit remarkable omp1 DNA sequence polymorphism, which can encourage for vaccine design and infection control.

Chlamydia Infections↗

PubMed1986

Host modification of the adherence properties of Chlamydia trachomatis.

The adherence of Chlamydia trachomatis LGV440(L1) to human HeLa 229 and mouse McCoy cells was stimulated by the lectin wheat germ agglutinin (WGA) and inhibited by the sugars N-acetyl-D-glucosamine, N-acetyl-D-galactosamine and chitobiose, but only when the chlamydiae had been passaged several times in HeLa cells. After passage in McCoy cells, the lectin and the sugars elicited little response. The non-LGV serovar UW-31(K), however, differed from LGV440(L1) in that, regardless of passage, the lectin and sugar effects were observed only in HeLa cells. Affinity chromatography on WGA-agarose confirmed that HeLa-grown LGV440(L1) bound to a significantly greater extent relative to McCoy-grown chlamydiae. In addition, participation of heterogeneous chlamydial ligands was suggested by the observation that the adherence of heated (60 degrees C, 5 min) UW-31(K) to HeLa cells at 37 degrees C was not inhibited at all, but at 5 degrees C, the adherence rate was greatly reduced, indicating the participation of heat-stable as well as heat-labile ligands. These data are interpreted to indicate that the passage history of C. trachomatis results in the acquisition of altered surface components that participate in the initial interaction of the bacterium with the host.

Animals↗

PubMed1988

Local antibody in semen for rapid diagnosis of Chlamydia trachomatis epididymitis.

Etiologic studies including micro-immunofluorescence serology for Chlamydia trachomatis were done on 45 consecutive men with acute epididymitis. Of the men 21, all less than 35 years old, had type specific Chlamydia trachomatis antibody in the semen. All patients with semen antibody also had Chlamydia trachomatis antibody in the serum, while only a few of the patients without semen antibody had serum antibody. Chlamydia antibody titers in the semen specimens were higher than those in the sera and they persisted longer. In only 1 patient with semen antibody was another potential etiological agent for epididymitis demonstrated, while most of the patients without semen antibody had bacterial causes for the epididymitis. It was concluded that measurement of Chlamydia trachomatis antibody in semen offered a noninvasive, sensitive and specific method, useful despite prior antibiotic therapy, for diagnosis of the etiology of epididymitis in young men.

Acute Disease↗

PubMedDate not supplied

A randomized trial to compare 7- and 21-day tetracycline regimens in the prevention of recurrence of infection with Chlamydia trachomatis.

Standard therapy for Chlamydia trachomatis in the United States consists of a 7-day course of tetracycline administration. Recurrent infections are frequent, however, in circumstances in which reinfection seems unlikely, suggesting that the standard regimen may be insufficient to cure the infection. It may reduce the number of organisms, however, below a detectable level at a test-of-cure visit. To evaluate recurrent infection, the authors studied patients with chlamydia who were treated with standard therapy, and they found a recurrence rate of 29% among 2,983 patients who returned to the clinic during a 2-year follow-up period. Recurrent infection was associated with younger age but was not related to either race or gender. To test the hypothesis that a longer treatment course might be more effective in preventing recurrent infection, the authors conducted a randomized trial that compared 7- and 21-day regimens of tetracycline administration. Of the 918 subjects enrolled in the trial, 220 were infected with C. trachomatis. The overall recurrence rate among patients who were infected and returned was 18.4% (9/49) in the 21-day group and 13.8% (8/58) in the 7-day group (P = .60). Similar results were obtained using survival analysis methods. Given the number of subjects who returned, this study had approximately a 65% statistical power to detect a reduction in recurrence rate, from 20% to 5%. Because of the similarity of the results in the two groups, it was concluded that 21 days of tetracycline administration is no more effective in preventing recurrence than 7 days of administration.

Adult↗

PubMed1993

Detection of Chlamydia trachomatis in semen by the polymerase chain reaction in male members of infertile couples.

OBJECTIVE: Our objective was to evaluate the presence of asymptomatic Chlamydia trachomatis infection by means of the polymerase chain reaction in male members of couples with previously undiagnosed infertility. STUDY DESIGN: Twenty-eight infertile-couples who had negative cultures or negative results when tested by deoxyribonucleic acid probe for Chlamydia trachomatis in semen and cervical samples were studied. Semen samples were tested for Chlamydia trachomatis by means of the polymerase chain reaction. Sera from both partners were diluted 1:128 and tested for immunoglobulin M antibodies to Chlamydia. Sera and ejaculated sperm were evaluated for the presence of antisperm antibodies. Semen analyses were also performed. RESULTS: Chlamydia trachomatis was identified in semen from 11 (39.3%) of the male partners. Its detection correlated with the presence in the ejaculate of motile sperm containing antisperm antibodies (p < 0.01). Either antisperm immunoglobulin G, immunoglobulin A, or both were located on sperm only from 5 (45.5%) of the 11 men whose results were positive when tested for Chlamydia trachomatis. Similarly, immunoglobulin G or immunoglobulin A antibodies to sperm were only detected in 5 (45.5%) of the spouses of men with Chlamydia in semen. Immunoglobulin M antibody to Chlamydia trachomatis was identified in only one of the men. However, antichlamydial immunoglobulin M antibodies were present in sera from 6 (54.5%) female partners of men with seminal Chlamydia trachomatis but in none of the other 17 women (p < 0.01). CONCLUSION: Although undetected by culture of deoxyribonucleic acid probe of semen samples, Chlamydia trachomatis was nevertheless identified in semen of some symptom-free men by the polymerase chain reaction. This is probably a result of the increased sensitivity of the polymerase chain reaction to detect Chlamydia trachomatis. The increased prevalence of an autoimmune response to sperm in men with this organism in their semen suggests that a subclinical chlamydial infection may activate an immune response to sperm. A similar association between Chlamydia trachomatis in semen and circulating antisperm antibodies in female partners indicates that Chlamydia may also induce an immune response to sperm in women. Infertility in these couples may be the result of a direct inflammatory response in the cervix or endometrium to repeated Chlamydia exposure or of the ability of Chlamydia to evoke an immune response to spermatozoa.

Adult↗

PubMed1994

Frequency of Chlamydia trachomatis in pregnant women.

Frequency of chlamydia trachomatis infection was investigated in eighty-five pregnant women by direct immunofluorescence (IF) and iodine staining methods. The overall frequency of true positive by both methods was 8.2%. Direct immunofluorescence method alone detected chlamydia infection in 16.5% women with 50% sensitivity and 93% specificity and by iodine method in 14.1% women with 58.3% sensitivity and 90.4% specificity. This shows that as compared to IF iodine method is more sensitive and less expensive and easier to perform. The frequency of chlamydia trachomatis infection in our study population appears to be age dependent with younger patients being more likely to be infected than the older patients.

Adult↗

PubMedDate not supplied

Perinatally acquired Chlamydia trachomatis associated morbidity in young infants.

OBJECTIVE: This study was designed to evaluate the spectrum of morbidity associated with perinatally acquired Chlamydia trachomatis in infants < or =12 weeks of age, and to determine its relationship to maternal Chlamydia trachomatis status. METHODS DESIGN: Retrospective review of maternal and infant records. SETTING: Large inner city teaching hospital. PATIENTS: A cohort of 530 symptomatic infants < or =12 weeks of age who were tested for Chlamydia trachomatis infection in the upper respiratory tract during a 2-year period from January 1993 to December 1994. RESULTS: During the study period, 70/530 (13.2%) patients tested positive for Chlamydia trachomatis from the conjunctiva and/or the nasopharynx. Complete medical records of 66 of these infants were available for review. Forty-eight of 66 (73%) infants had conjunctivitis, 13/66 (20%) had pneumonia, 5/66 (7%) had both conjunctivitis and pneumonia. Thirteen of 66 (20%) infants were hospitalized, 7 for pneumonia and 6 for ophthalmia, accounting for 68 hospital days. In 55/66 (83%), maternal records were available for review. Nineteen of 55 (35%) mothers had documented Chlamydia trachomatis infection at delivery or during pregnancy that had not been treated; 16/55 (29%) mothers tested negative for Chlamydia trachomatis sometime during pregnancy but were not retested at delivery, 8/55 (14%) were treated for Chlamydia trachomatis during pregnancy but status at delivery regarding reinfection was not evaluated. In 12/55 (22%) mothers, no prenatal testing was documented. CONCLUSIONS: This study demonstrates significant morbidity in early infancy associated with perinatally acquired Chlamydia trachomatis infection. There is need for studies evaluating the importance of adequate maternal testing and treatment to reduce perinatal transmission.

Chlamydia Infections↗

PubMed1992

PCR detection and differentiation of Chlamydia pneumoniae, Chlamydia psittaci and Chlamydia trachomatis.

A PCR-based system was developed for the detection and differentiation of Chlamydia trachomatis, Chlamydia psittaci and Chlamydia pneumoniae. A conserved 145 bp fragment of the chlamydial omp1 gene was amplified from all three species. The three species were then differentiated from each other by digestion of this PCR product with restriction enzymes Eco RI and either Hind III or Pst I. The system was shown to work for two strains of C. pneumoniae, 11 strains of C. psittaci and 10 serovars of C. trachomatis, and had a sensitivity of less than 10 chlamydial elementary bodies. This method was also applicable to the detection of C. trachomatis in conjunctival and nasopharyngeal swabs.

Adult↗

PubMed1999

Evaluation of vaginal introital sampling as an alternative approach for the detection of genital Chlamydia trachomatis infection in women.

BACKGROUND: Genital Chlamydia trachomatis infections in women are traditionally detected by testing cervical and urethral samples. This sampling approach is not acceptable in some, e.g. screening situations. We evaluate an alternative approach, i.e. use of vaginal self-collected specimen for testing by polymerase chain reaction. METHODS: The sensitivity of self-collected vaginal (introital) samples to diagnose genital infections by Chlamydia trachomatis using Roche AMPLICOR CT/NG PCR was compared with the cervical- and first-voided urine samples from women consulting with- (Group 1; n=123) and without (Group 0; n=160) genital symptoms. Women were interviewed regarding genital hygiene. Genital symptoms and signs were noted. RESULTS: C. trachomatis DNA was detected in 13.0% of women from Group 1 and in 5.0% of women from Group 0, i.e. in urine of 6.5% vs. 1.9%, in the cervical swab in 9.8% vs. 5.0% and in vaginal swab in 11.4% vs. 3.8% of women, respectively. The vaginal sample was the most sensitive specimen for detecting C. trachomatis in the Group 1 women. It had sensitivity of 87.5% vs. 75% for cervical- and 50% for urine specimens. In Group 0, the cervical sample was 100% sensitive, while the vaginal introital sample and urine had a sensitivity of 75% and 37.5%, respectively. C. trachomatis was less often detected in urine of women who routinely practised genital washing. CONCLUSIONS: Vaginal sampling performed by the woman herself is a sensitive approach and might serve as an important stimulus for screening for C. trachomatis infections in young women at risk.

Adolescent↗

PubMed1988

The role of Chlamydia trachomatis in Bartholin's gland abscess.

Chlamydia trachomatis is becoming increasingly known for its ability to cause severe injury to the female genital tract. Little investigation has been done in its role in diseases of Bartholin's glands. We present what we believe to be the first case report of an abscess of a Bartholin's gland in which Chlamydia trachomatis was a major pathogen. This communication also review the literature concerning the microbiology of Bartholin's gland abscess.

Abscess↗

PubMed1997

[Polymerase chain reaction in the detection of patients infected by Chlamydia trachomatis after treatment].

OBJECTIVE: To investigate the value of polymerase chain reaction (PCR) for follow-up patients infected by Chlamydia trachomatis. METHODS: Follow-up specimens were collected from 30 patients. Chlamydia trachomatis positive were detected by PCR and direct fluorescence assay test (DFA) in the 30 patients before therapy. 15 patients were treated with minocycline (100 mg twice daily) for 10 days, and 15 patients were treated with 1.0 g of azithromycine as a single oral dose. RESULTS: After 1-2 weeks of antimicrobial therapy, all patients had negative DFA for Chlamydia trachomatis, but 9 had positive Chlamydia trachomatis DNA as detected by PCR. CONCLUSIONS: The 9 specimens were not confirmed to livae viable organisms of Chlamydia trachomatis. The debris of nonviable Chlamydia trachomatis DNA was excluded from urinogenital tract at about one month.

Adult↗

PubMedDate not supplied

Chlamydia trachomatis infection in sexually active adolescents and young women.

BACKGROUND: The prevalence of Chlamydia trachomatis infections among Polish teenagers is unknown. Sexually active adolescents are at a greater risk for sexually transmitted infections, including Chlamydia trachomatis (ChT). Most inflections are asymptomatic and therefore untreated. Early detection and treatment of cervical chlamydial infections can prevent pelvic inflammatory disease and has a strong protective effect against infertility. AIM: To determine the prevalence and risk factors of Chlamydia trachomatis infections among sexually active female adolescents attending the outpatient gynaecological clinic of the Institute of Mother and Child in Warsaw. MATERIALS AND METHODS: 249 sexually active girls, 16-19 years old, attending the outpatient clinic of the Institute of Mother and Child in Warsaw were enrolled in this study from December 2002 to May 2004, The participants filled out a questionnaire containing informations on age, purpose of the visit, level of education, age of the first intercourse, number of lifetime sexual partners, number of current partners (in the last 3 months), number of sexual partners in the past (patients' partner), contraceptive methods, use of condoms at the first and the last intercourse, past history of STD and obstetric history at first visit. Pelvic examination was done for the following reasons: checking vaginal discharge, presence of abnormalities of the cervix such as ectopy, erythroplakia and uterine tenderness and taking a Pap smear and a cervical swab for Chlamydia trachomatis detection. Cervical swabs for Chlamydia trachomatis were tested by Polymerase Chain Reaction (PCR). RESULTS: The prevalence of ChT genital infection in the studied group was 3.2%. Adolescent females infected by ChT less frequently reported the use of condom and more often did not use any contraception in comparison with the girls without ChT genital infections (42.8% and 42.8% vs. 49% and 12.8%), The existence of other STDs was more frequently noted in adolescents with Chlamydial infection in comparison to healthy girls (14.2% vs. 8.3%). There were no statistically significant differences in results of the Pap smears and the incidence of cervical ectopy between the two groups.

Adolescent↗

PubMed1997

Performance and cost-effectiveness of selective screening criteria for Chlamydia trachomatis infection in women. Implications for a national Chlamydia control strategy.

BACKGROUND AND OBJECTIVES: Detection of subclinical Chlamydia trachomatis infection in women is a high but costly public health priority. GOALS: To develop and test simple selective screening criteria for chlamydia in women, to assess the contribution of cervicitis to screening criteria, and to evaluate cost-effectiveness of selective versus universal screening. STUDY DESIGN: Cross-sectional study and cost-effectiveness analysis of 11,141 family planning (FP) and 19,884 sexually transmitted diseases (STD) female clients in Washington, Oregon, Alaska, and Idaho who were universally tested for chlamydia using cell culture, direct fluorescent antibody, enzyme immunoassay, or DNA probe. RESULTS: Prevalence of cervical chlamydial infection was 6.6%. Age younger than 20 years, signs of cervicitis, and report of new sex partner, two or more partners, or symptomatic partner were independent predictors of infection. Selective screening criteria consisting of age 20 years or younger or any partner-related risk detected 74% of infections in FP clients and 94% in STD clients, and required testing 53% of FP and 77% of STD clients. Including cervicitis in the screening criteria did not substantially improve their performance. Universal screening was more cost-effective than selective screening at chlamydia prevalences greater than 3.1% in FP clients and greater than 7% in STD clients. CONCLUSIONS: Age and behavioral history are as sensitive in predicting chlamydial infection as criteria that include cervicitis. Cost-effectiveness of selective screening is strongly influenced by the criteria's sensitivity in predicting infection, which was significantly higher in STD clients. At the chlamydia prevalences in the populations studied, it would be cost saving to screen universally in FP clinics and selectively in STD clinics, the reverse of current practice in many locales.

Adolescent↗

PubMed2001

Managing genital chlamydia trachomatis infection in Scotland: targeted opportunistic testing or a screening programme?

OBJECTIVE: To compare two models of testing for genital chlamydia trachomatis infection: opportunistic testing for genital chlamydia trachomatis at sexual health related consultations, as advocated in the SIGN guideline on Chlamydia trachomatis, or the introduction of a screening programme. DESIGN: Calculation of estimates of numbers of cases found in one Health Board Area using the two different approaches. Review of the literature on chlamydia with reference to the UK National Screening Committee criteria for appraisal of a screening programme. SETTING: Lothian Health Board Area. RESULTS: The evidence suggests that a screening programme for chlamydia has population benefits and is cost effective compared to a no-screening approach. However, current understanding of the natural history of chlamydial infection and the effect of treatment is inadequate to fully inform individual women regarding the benefit of testing. Full implementation of the SIGN guideline on Chlamydia trachomatis in Lothian would detect at least 600 new cases of chlamydia whereas a screening programme would detect over 2000 new cases in the first year. CONCLUSION: Opportunistic testing at sexual health related consultations does not equate with a screening programme. Although a screening programme would detect more cases of chlamydia trachomatis its cost effectiveness compared to opportunistic testing is unproven. Introducing a screening programme has individual psychological and broader social and ethical implications and must not occur by default.

Adolescent↗