Sexually Transmitted Diseases in Pediatrics

Abstract

The scope of this chapter would be describing bacterial sexually transmitted diseases that are of interest in pediatric population such as gonorrhea and syphilis. Currently, this diseases has been reported an increased incidence mostly in adolescents in different regions around the world such as Australia and United States. These diseases sometimes considered anecdotal are always difficult to manage because they are considered taboos; diagnosis and treatment are challenging because of the interaction with the child and his/her parents. Other diseases such as chlamydia are also taking a great importance in populations from 10 to 24 years old due to the high transmission, high incidence, and complications such as infertility, almost 80% or chlamydia infections are asymptomatic in women being one of the leading causes of infertility that could be permanent. In this chapter, we will be discussing about the main factors of this diseases, how to manage from pediatric perspective, the most novel diagnostic tests and treatments (if available), and any vaccine development possibilities.

1. Introduction

Sexually transmitted diseases (STDs) surveillance is key to understand the surveillance and the burden of these diseases in pediatrics. In this chapter, we will be presenting the key features of bacterial sexually transmitted diseases in general and focus on the pediatric population. Pediatric aspects of sexually transmitted diseases are important because these are the basis for the development of new public health tools for prevention. Most of these diseases can be treated; nevertheless, the continuous use of antibiotic therapy is already giving trouble with antibiotic resistance as it is the case of gonorrhea. New generations have a more open sexual behavior and are also starting earlier sexual contacts, which makes crucial the development of new ways of sexual education and the development of vaccines that can be started in younger populations.

2. Epidemiology

In 2016, the World Health Organization (WHO) estimated the global prevalence and incidence of bacterial sexually transmitted diseases in population from 15 to 49 years of age; for this estimation, almost 130 studies were reviewed. The estimated prevalence for Chlamydia, Trichomonas, Syphilis, and Gonorrhea taking into account the prevalence data from 2009 to 2016 and per gender is presented in Table 1. The prevalence of these diseases is inversely proportional to the income in the countries and regions; with higher incomes, the prevalence goes lower. Incidence of these pathogens per gender is presented in Table 2 [1].

Gender	WHO 2016 estimated global prevalence, % (95% UI-uncertainty index)
	Chlamydia	Gonorrhea	Trichomoniasis	Syphilis
Women	3.8 (3.3–4.5)	0.9 (0.7–1.1)	5.3 (4.0–7.2)	0.5 (0.5–0.6)
Men	2.7 (1.9–3.7)	0.7 (0.5–1.1)	0.6 (0.4–0.9)	0.5 (0.4–0.6)

Table 1.

2016 WHO prevalence estimates of chlamydia, gonorrhea, Trichomoniasis, and syphilis, global by gender.

Gender	WHO 2016 estimated global incidence, cases per 1000 (95% UI-uncertainty index)
	Chlamydia	Gonorrhea	Trichomoniasis	Syphilis
Women	34 (25–45)	20 (14–28)	40 (27–58)	1.7 (1.4–2.0)
Men	33 (21–48)	26 (15–41)	42 (23–69)	1.6 (1.3–1.9)

Table 2.

2016 WHO incidence estimates of chlamydia, gonorrhea, Trichomoniasis, and syphilis, global by gender.

In the 2020 National Surveillance of STDs in the United States, a total of 1,579,885 cases of Chlamydia trachomatis infection were reported to the CDC, making it the most common notifiable sexually transmitted infection in the United States for that year. This case count corresponds to a rate of 481.3 per 100,000 population; for syphilis, 133,945 cases were reported including 41,655 cases of primary and secondary syphilis, the most infectious stages of the disease. Since 2000, rates of primary and secondary syphilis have increased among men, likely attributable to increases in cases among men having sex with men (MSM). For Gonorrhea, a total of 677,769 cases were reported do the CDC, making it the second most common notifiable sexually transmitted infection in the United States for that year. In the case of Trichomoniasis, in 2018, 2.6 million infections were reported; this pathogen can increase the risk of HIV and preterm deliveries with low birth weight. The prevalence of Trichomonas vaginalis in the United States is 2.1% among women aged 14–59 and 0.5% among men (representative sample from 2013 to2016). If we compare 2016 report with the 2020 report, it seems that there was a decrease in the number of cases; but this is indeed an artifact due to COVID-19 pandemic. Even in the face of COVID-19, an important number of STDs were reported; [2, 3] number of cases by selected groups of age and from this survey (Trichomoniasis was not included) are presented in Table 3.

Age group (years)	Rates per 100,000 of reported cases by age group, gender, and disease; United States, 2020
	Chlamydia		Gonorrhea		Syphilis
	Male	Female	Male	Female	Male	Female
10–14	11.3	85.4	5.5	23.3	0.1	0.2
15–19	846.3	2857.9	369.0	616.4	10.9	5.9
20–24	1627.3	3729.6	821.5	866.9	43.5	14.3
25–29	988.3	1548.0	727.9	505.3	58.1	14.4
30–34	611.7	713.3	567.6	312.3	55.7	13.0
35–39	340.7	332.3	357.4	180.6	39.4	9.1
40–44	203.3	168.5	240.3	101.5	29.9	7.3
45–54	98.8	59.7	124.7	37.0	21.0	3.4
55–64	38.7	16.5	57.0	9.4	11.4	0.9
65+	6.4	2.0	10.3	1.1	2.1	0.1
Total	339.4	616.5	238.5	174.5	20.8	4.7

Table 3.

Sexually transmitted disease CDC surveillance 2020 (adapted from the CDC report, division of STD prevention).

From Table 3, Chlamydia, Gonorrhea, and Syphilis cases start rising at 15 years of age; with the highest peak from 20 to 24 years of age; 25–29 years, it is still higher, and the cases start to decline at 30 years of age and keep decreasing. This epidemiological behavior is the basis of the development of public health measurements, treatment, and eventually, vaccine development.

3. The pathogens

Bacteria causing STDs have similar features related to their biology and mechanisms of infection. C. trachomatis (CT) is a Gram-negative obligate intracellular bacterium discovered in 1907, humans are its exclusive natural host; serovars associated with sexually transmitted infection are D–K. Chlamydiae are obligate intracellular bacteria with two development forms, the infectious elementary body (EB) and the active division body that is not infectious, reticulate body (RB). Once a cell is infected, the EBs can differentiate to RBs, and after a cycle of around 2 days, more EBs can be released by lysis of the host cell or by the active release of inclusions [4, 5, 6, 7]. Neisseria gonorrhea (Ng) is also a Gram-negative bacterium obligated human pathogen described for the first time by Albert Neisser on 1879. CDC provides data on reported gonorrhea morbidity since the 1940s. Ng has evolved mechanisms for evading innate immunity and suppressing adaptive immune responses, like CT [8, 9, 10].

Syphilis pathogen is a spirochaete, Treponema pallidum (Tp); analysis based on the mutation rates of this pathogen suggests that venereal syphilis diverged several thousand years ago from Africa; this contradicts the Columbian hypothesis, in which the idea was that the shipmates of Christopher Columbus “Cristóbal Colón” brought the newly evolved venereal disease from the New World into Western Europe in the late fifteenth century; again like CT and Ng, Tp is an obligate human pathogen [11, 12].

Even the title of this chapter refers to bacterial STDs, Trichomonas vaginalis (Tv) deserved to be included since it is the most prevalent curable STD globally. Tv is a flagellated protozoan parasite of the human genital tract. Tv has no cystic stage in its life cycle, four anterior flagella provide the parasite its characteristic motility, and its single posterior flagellum assists the motility of extracellular nutrients toward the cytosome of the cell [13].

4. The disease

4.1 Pathogenesis and transmission

All the included pathogens are highly transmissible, one of the most important features for this is that most of the infected people, mostly women, remain asymptomatic and do not seek treatment. All of these diseases are transmitted during sexual intercourse.

CT can avoid destruction by the host’s innate and adaptive immune systems by autophagy, which allows CT to migrate to the upper genital tract for establishing a chronic infection. Without treatment, up to 50% of infected women will continue to be infected for greater than 1 year. CT can be in the semen of infected males or can be released from infected female genital tract epithelial cell. CT can bind to almost all receptors in the epithelial cell (i.e. mannose, mannose-6-phosphate, epidermal growth factor, B1 integrin, platelet-derived growth factor receptor, protein disulfide isomerase, fibroblast growth factor receptor, and ephrin receptor A2). CT induces actin remodeling that facilitates the entry in the cytoplasm. The EBs are internalized in vacuoles and form an intracytoplasmic inclusion, which can evolve to RBs, these RBs are the non-infectious replicative form and use nutrients within the host cytoplasm and replicate by binary fission, when the RB-filled inclusion reaches critical volume, RBs convert back to EBs, and they can be released to the extracellular milieu by two mechanisms: host lysis or extrusion of the cytoplasmic inclusion [4, 14].

Ng affects the urogenital tract, mostly the columnar and transitional epithelia. Ng prevents complement activation, opsonization, and bacterial killing. Ng prevents complement activation, opsonization, and bacterial killing and can survive in and around the macrophages and neutrophils during infection and modulate the immune-activating properties of dendritic cells. Ng infection does not generate immunological memory, owing to the ability of Ng antigenically and phase vary its surface structures. In men, Ng attaches to sperm, which is easily transmitted from men to their partners through ejaculates with high number of bacteria. In women, bacterial sialidases, which are secreted by the cervicovaginal microbiota of women, must first desialylate Ng lipooligosaccharide to enable efficient transmission [10].

In the case of Tp, the mechanisms of tissue damage by Tp are still not well described. The local inflammation process has been attributed to the spirochete itself; nevertheless, the fragility and low protein content of its outer membrane make it very difficult to well characterize them. A well definition of protective immunity is still unavailable. Transmission of venereal syphilis occurs during sexual contact with an actively infected partner, same as the other three diseases described in this chapter; with only 10 organisms in the exudate, the disease can be transmitted. Tp can penetrate directly the mucous membranes and adhere to the epithelial cells and extracellular matrix components for establishing the infection, fibronectin and laminin are key for Tp interactions with the cell. The infection becomes systemic very fast, once the blood–brain barrier is reached (this happens in as many as 40% of individuals with syphilis), early syphilis without treatment can cause severe neurological complications [12].

Tv transmission occurs almost exclusively via sexual contact, even some transmission via fomites has been argued, which is highly controversial and lacks strong evidence. During sexual intercourse, Tv in the genital tract of the infected partner is transferred to the uninfected partner, when Tv reaches the epithelial cells, Tv assumes an ameboid form increasing its surface area contact. The five primary surface adhesins responsible for the attachment of the parasite to the epithelia are AP120, AP65, AP51, AP33, and AP23. Iron is the most important mediator of Tv growth [13].

4.2 Clinical manifestations

It can be said that all these diseases have similar clinical manifestations including purulent exudates in male urethra and female cervix and urinary tract infection manifestations. Also, one common feature is that all of them can be asymptomatic, at least for some time. Common clinical manifestations are presented in Table 4 for comparison purposes. Special characteristics are described in the next subsections.

Clinical manifestation	CT	Ng	Tp	Tv
Can be asymptomatic?	Yes, very frequent mainly in females	Yes, very frequent mainly in females	Varied and often subtle manifestations, it is called the Great Imitator. First manifestation could be a single ulcer (chancre) or multiple lesions typically painless with regional lymphadenopathy ∼3 weeks post-infection that resolves spontaneously	Yes in 50% of the cases and around 30% of them can develop some symptoms in the 6-month period postinfection
Itching, pain during intercourse, frothy discharge, vaginitis in women, mild to severe and urethritis with purulent discharge in men; urinary tract infection symptoms in both	Yes	Yes	No	Yes, In acute cases, punctate hemorrhagic spots may be present on the vaginal and cervical mucosa (colpitis macularis, or “strawberry cervix”)
Pelvic inflammatory disease	Yes	Yes	No	Yes
Cervical cancer association	No	No	No	Yes
Infertility	Yes	Yes	Yes	Yes
Vertical transmission?	Yes	Yes	Yes	Yes
Extragenital infections are present	Yes (pharyngitis and proctitis)	Yes (pharyngitis and proctitis)	Ocular syphilis and Otosyphilis can occur at any stage but is commonly identified during the early stages and can present with or without additional Central Nervous System involvement
Other special features	Co-infection with Ng is frequent	Co-infection with CT is frequent	Ocular syphilis can result in permanent vision loss.; Otosyphilis typically presents with cochleo-vestibular symptoms, including tinnitus, vertigo, and sensorineural hearing loss. Hearing loss can be unilateral or bilateral, have a sudden onset, progress rapidly, and can result in permanent hearing loss

Table 4.

Common clinical features of sexually transmitted diseases (CT, ng, Tp, and Tv).

Congenital Syphilis	Physical examination	Serum non-treponemal serologic test	Dark field test or PCR of placenta, cord, lesions, or body fluids	Silver stain of the placenta or cord	Recommended evaluation
Proven or highly probable	Abnormal and consistent with congenital syphilis	Fourfold or greater, higher than the mother’s titer at delivery	Positive	Positive	Cerebrospinal fluid (CSF) analysis for VDRL, cell count and protein.; Complete blood count (CBC) and differential and platelet count.; Long-bone radiographs
Possible	Normal	Equal to or less than fourfold of the maternal titer at delivery*	NA	NA
Less Likely	Normal	Equal to or less than fourfold of the maternal titer at delivery**	NA	NA	No evaluation is recommended
Unlikely	Normal	Equal to or less than fourfold of the maternal titer at delivery***	NA	NA

Table 5.

Congenital syphilis possibilities.

*

And one of the following: mother was not treated (inadequately or not documented), mother was treated with erythromycin or a non-penicillin G regimen, mother with an adequate treatment but started <30 days before delivery.

**

And both of the following are true: Mother was treated adequately for infection stage during pregnancy, and treatment was started ≥30 days before delivery, and mother has no evidence of reinfection or relapse.

***

And both of the following are true: mother’s treatment was adequate before pregnancy, and the mother’s non-treponemal serologic titer remained low and stable before and ruing pregnancy and at delivery.

4.2.1 Chlamydia in pediatrics

4.2.1.1 Chlamydia neonatorum

Chlamydia can be presented in different age groups in pediatrics. In the neonate, it is also known as Chlamydia neonatorum. Infection in neonates results from perinatal exposure to the mother’s infected cervix. Initial infection involves the mucous membranes of the eye, oropharynx, urogenital tract, and rectum, although infection might be asymptomatic in these locations. The most common manifestation in neonates is conjunctivitis that develops 5–12 days after birth. Nowadays, this infection is much less frequent due to widespread prenatal screening and treatment of pregnant women.

4.2.1.2 Chlamydial pneumonia among infants

This type of pneumonia typically occurs at age 1–3 months and is a subacute pneumonia. Characteristic signs include a repetitive staccato cough with tachypnea and hyperinflation and bilateral diffuse infiltrates on a chest radiograph. Peripheral eosinophilia (≥400 cells/mm3) occurs frequently. Considering that this clinical presentation is broad, symptoms of pneumonia in infants aged 1–3 months and especially those whose mothers have a history of are at risk for or suspected of having a chlamydial infection should be tested for C. trachomatis and treated if infected. Mothers at risk include aged <25 years and those aged ≥25 years who have a new sex partner, more than one sex partner, a sex partner with concurrent partners, or a sex partner who has or had a sexually transmitted disease/infection.

4.2.2 Neisseria gonorrhea in pediatrics

4.2.2.1 Neisseria gonorrhea in neonates

In the neonatal period, infections due to Ng result from perinatal exposure to the infected cervix of the mother.

Ophthalmia neonatorum can result in perforation of the globe of the eye and blindness. Newborns at increased risk for gonococcal ophthalmia include those who did not receive ophthalmic prophylaxis and whose mothers had no prenatal care, have a history sexually transmitted infections or history of substance abuse. A Gram stain of the conjunctival exudate will be very helpful for a strong suspicion under the finding of intracellular Gram-negative diplococci. This finding can justify the treatment for gonorrhea, appropriate cultures and antimicrobial susceptibility testing for Neisseria gonorrhoeae will be required.

Neonates can develop disseminated gonococcal infection that can be presented as sepsis, arthritis, or meningitis. It is a rare complication of neonatal gonococcal infection. Localized gonococcal infection of the scalp can result from fetal monitoring through scalp electrodes. Detecting gonococcal infection when suspected in neonates will require cultures of blood, cerebrospinal fluid, or joint aspirate. Positive Gram-stained smears of different specimens are considered strong evidence for initiating treatment for Ng.

Another important consideration is neonates born to mothers with untreated gonorrhea. These neonates should be tested and treated for Ng.

4.2.3 Syphilis

Special considerations for Syphilis must be taken considering the different clinical stages at presentation. Primary syphilis classically presents as a single painless ulcer or chancre at the site of infection but can also present with multiple, atypical, or painful lesions. Secondary syphilis manifestations can include skin rash, mucocutaneous lesions, and lymphadenopathy. Tertiary syphilis can present with cardiac involvement, gummatous lesions, tabes dorsalis, and general paresis. Latent infections are those lacking clinical manifestations and are detected by serologic testing; if this was acquired within the preceding year it is referred to as early latent syphilis; all other cases of latent syphilis are classified as late latent syphilis or latent syphilis of unknown duration [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16].

4.2.3.1 Syphilis in pediatrics

Infants and children aged ≥1 month with diagnosis of syphilis required to be evaluated for determine if syphilis is congenital or acquired, when primary or secondary syphilis is determined, children need to be evaluated by an interdisciplinary group including a general pediatrician, an pediatric infectious disease specialist, psychologist, social workers, and other specialists depending on the required treatment. Sexual abuse must be investigated.

In the case of latent syphilis, cerebrospinal fluid must be evaluated in addition to the considerations done for primary and secondary.

4.2.3.1.1 Congenital syphilis

Maternal risk factors for syphilis during pregnancy include sex with multiple partners, sex in conjunction with drug use or transactional sex, late entry to prenatal care or no prenatal care, methamphetamine or heroine use, incarceration of the woman or her partner, and unstable housing or homelessness.

All neonates born to mothers who have reactive non-treponemal and treponemal test results should be evaluated with quantitative non-treponemal serologic test performed on the neonate’s serum (umbilical cord blood has to be avoided due to the presence of maternal blood), and Wharton’s jelly could lead to a false-negative result. Depending of the congenital syphilis possibilities (confirmed proven or highly probable, possible, less likely, unlikely), different treatment doses can be recommended. Congenital Syphilis possibilities are presented in Table 5, treatment is described in the corresponding section.

4.3 Diagnosis

As we previously described, many clinical features are common to these diseases, when suspected laboratory confirmation is expected and required.

4.3.1 C. trachomatis and Neisseria gonorrhea

In the case of CT and Ng, we can speak about the type of technologies for diagnosis: batch testing in a laboratory and point-of-care testing as single tests. Currently, the gold standard for the diagnosis of both diseases is the Nucleic Acid Amplification Tests (NAATs). These tests are designed to amplify nucleic acid sequences that are specific for the organism being detected and do not require viable organisms. These kinds of tests can detect even a single copy of the target DNA or RNA. Most important features of batch testing for CT and Ng are included in Table 6 [15].

Type	Test	CT	Ng
Batch Testing	Culture	48–72 hours of growth; High variability and low sensitivity; Not for diagnosis	To be examined at 24 hour interval for ≤72 hours; Even the high sensitivity and specificity, a very good transportation is required; Not for diagnosis
	Nucleic acid amplification tests (NAATs)	(Common to CT and Ng); Gold standard for diagnosis; Can detect CT and Ng in: Endocervical swabs from women,; Urethral swabs from men,; Urine from both men and women
		CT; Commercial NAATs are not known to cross-react with DNA from other bacteria in humans	Ng; Some NAATs might cross-react with nongonococcal Neisseria species
	Nucleic acid hybridization (Nucleic Acid Probe) Tests	These tests can detect both pathogens in a single specimen.; These tests do not differentiate between the 2 organisms, when positive tests for each organism are needed; Advantage: store and transport have a maximum of 7 days without refrigeration
	Serology tests	Should not be used for screening	A serologic screening or diagnostic assay is not available

Table 6.

Batch testing diagnostic tests for CT and ng.

In the case of CT, point-of-care-tests can be performed within 30-minute delivering qualitative results. For Ng, the current point-of-care test is the Gram stain, this is mostly used in men (urethral exudates); in the case of women, the Gram stain has low sensitivity; therefore, it is not recommended in women.

4.3.1.1 C. trachomatis diagnostic considerations among infants and children

NAATs can be used to test vaginal and urine specimens from girls and urine in boys. There are not enough data about using NAATs for specimens from extragenital sites; nevertheless, there is no evidence supporting that NAAT performance would differ from that among adults. Because of the implications, only validated NAAT tests must be used for diagnosing CT in extragenital sites.

4.3.1.2 Neisseria gonorrhea diagnostic considerations among infants and children

Culture and NAATs can be used to test urogenital and extragenital sites in children. Same as CT, only validated NAAT tests must be used for the diagnosis of Ng in samples coming from extragenital sites. It will be very important to take into account the potential cross-reaction with non-gonococcal Neisseria (i.e., Neisseria meningitidis, N. sicca, Neisseria lactamica, N. cinerea) and other commensals (Moraxella catarrhalis) for an adequate interpretation of the results.

Gram stains are not recommended in prepuberal children for diagnosis, must NOT be used. In the case of disseminated Ng, culture and antimicrobial susceptibility testing should be obtained from the relevant clinical sites.

4.3.2 Trichomonas vaginalis

Even wet-mount microscopy has been used as the preferred diagnostic test for Trichomonas vaginalis, it is true that with the development of more highly sensitive and specific molecular tests, now the best option is NAATs (98.3% and 99.6%, respectively). Reliable samples include endocervical and vaginal swabs collected by clinicians, female urine specimens, and liquid Pap smear specimens [3].

4.3.3 Syphilis

Darkfield examinations and molecular testes for detecting Tp are the definitive methods for early syphilis and congenital syphilis diagnosis. These tests can be done from material collected directly from the lesion exudate or tissue. Commercial NAATs are not available; nevertheless, some laboratories can provide developed and validated PCR tests.

For a presumptive diagnosis of Syphilis, two types of tests are required:

A Non-treponemal test:

• VDRL (venereal disease research laboratory)

OR

• Rapid plasma reagin (RPR)

AND

A Treponemal test.

Diagnosis of syphilis can start either with a non-treponemal or a treponemal test.

When the first test is a non-treponemal one, confirmation with a treponemal test is always required due to the multiple medical conditions that could result in a false-positive nontreponemal test; some of these are HIV, autoimmune conditions, vaccines, injecting drug use, pregnancy, and older age. Nontreponemal test antibody titers are useful for monitoring treatment response.

If diagnosis of syphilis is established starting with a treponemal test, a quantitative non-treponemal test will be needed for patient management decisions. If non-treponemal test is negative, then the treponemal assay needs to be repeated, this should be different from the one used for initial testing.

Flow of non-treponemal and treponemal tests for decision-making is presented in Figure 1.

Figure 1.

Traditional and reverse algorithms for syphilis diagnosis.

4.4 Treatment

An important characteristic of these pathogens is the presence of available treatment; nevertheless, antibiotic resistances are becoming a bigger issue every day for Ng. In the case of CT, event with available treatment, many cases are asymptomatic; therefore, available treatment is covering this public health issue partially. Special considerations for pediatrics must be taken into account mostly for Gonorrhea. In Table 7, we are presenting the current treatment guidelines per each pathogen [2, 16].

Treatment	CT	Ng	Tp	Tv
Affected patient	Neonates: Oral erythromycin base or ethyl succinate 50 mg/kg body weight/day divided into 4 doses daily for 14 days; Chlamydial Pneumonia Among Infants: oral erythromycin base or ethyl succinate 50 mg/kg body weight/day orally; divided into 4 doses daily for 14 days (alternative regimen: oral azithromycin suspension 20 mg/kg/day, 1 dose daily for 3 days); Infants and children: Weighing <45 kg: Erythromycin base or ethyl succinate 50 mg/kg body weight/day orally divided into 4 doses daily for 14 days; Weighing ≥45 kg but aged <8 years: Azithromycin 1 g orally in a single dose; Children aged ≥8 years: Azithromycin 1 g orally in a single dose; OR; Doxycycline 100 mg orally 2 times/day for 7 day; Adolescents and Adults: Oral Doxycycline 100 mg 2 times per day for 7 days; Alternative regimens: Oral Azithromycin 1 g, single dose; OR; Oral Levofloxacin 500 mg once daily for 7 days; Pregnancy: Oral Azithromycin 1 g, single dose (alternative: oral Amoxicillin 500 mg 3 times a day for 7 days	Adult and Adolescents: Uncomplicated Gonococcal Infection of the Cervix, Urethra, or Rectum: Ceftriaxone 500 mg Intramuscular (IM) in a single dose for persons weighing <150 kg (If ≥150 kg, 1 g ceftriaxone).; Alternatives if ceftriaxone is not available: Gentamicin 240 mg IM in a single dose plus Azithromycin 2 g orally in a single dose; OR; Cefixime 800 mg orally in a single dose; Uncomplicated gonococcal infection of the pharynx: Ceftriaxone 500 mg IM in a single dose for persons weighing <150 kg (if ≥150 kg, 1 g ceftriaxone).; Gonococcal Conjunctivitis; Ceftriaxone 1 g IM in a single dose (one time lavage of the infected eye with saline solution must be considered); Gonococcal-Related Arthritis and Arthritis-Dermatitis Syndrome; Ceftriaxone 1 g IM or IV every 24 hours (alternative regimen: Alternative Regimens Cefotaxime 1 g IV every 8 hours or Ceftizoxime 1 g every 8 hours); Neonates, Infants and Children; Ophthalmia Neonatorum PREVENTION: Erythromycin 0.5% ophthalmic ointment in each eye in a single application at birth; Ophthalmia Neonatorum TREATMENT: Ceftriaxone 25–50 mg/kg body weight IV or IM in a single dose, not to exceed 250 mg; Disseminated Gonococcal Infection Among Neonates: Ceftriaxone 25–50 mg/kg body weight/day IV or IM in a single daily dose for 7 days, with a duration of 10–14 days if meningitis is documented; OR; Cefotaxime 25 mg/kg body weight/day IV or IM every 12 hours for 7 days, with a duration of 10–14 days if meningitis is documented; Neonates without signs of gonococcal infection: Ceftriaxone 20–50 mg/kg body weight IV or IM in a single dose, maximum 250 mg; Uncomplicated Gonococcal Vulvovaginitis, Cervicitis, Urethritis, Pharyngitis, or Proctitis Among Infants and Children: Weighing ≤45 kg: Ceftriaxone 25–50 mg/kg body weight IV or IM in a single dose, not to exceed 250 mg IM; Weighing >45 kg: same as adults; Bacteremia or Arthritis Among Children: Weighing ≤45 kg: Ceftriaxone 50 mg/kg body weight (maximum dose: 2 g) IM or IV in a single dose daily every 24 hours for 7 days; Weighing >45 kg: Ceftriaxone 1 g IM or IV in a single dose daily every 24 hours for 7 days	Parenteral Penicillin G (dosage and length of the treatment depend on the stage and clinical manifestations); Congenital Syphilis: Confirmed or highly probable: Aqueous crystalline penicillin G 100,000–150,000 units/kg/body weight per day, administered as 50,000 units/kg/body weight per dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days; OR; Procaine penicillin G 50,000 units/kg/body weight per dose IM in a single daily dose for 10 days; Possible: Same as confirmed with and additional option of Benzathine penicillin G 50,000 units/kg body weight/dose IM in a single dose; Less Likely and unlikely: Benzathine penicillin G, same doses as possible.; Infants and children: Benzathine penicillin G 50,000 units/kg body weight IM, up to the adult dose of 2.4 million units in a single dose; Adults: Primary, Secondary and Early latent: Benzathine penicillin G 2.4 million units IM in a single dose; Late latent: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals; Tertiary: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals	Women: Metronidazole 500 mg orally 2 times/day for 7 days; Men: Metronidazole 2 g orally in a single dose; Alternative regimen for women and men: Tinidazole 2 g orally in a single dose
Sex partners	Sex partners should receive treatment if they had sexual contact with the partner during the 60 days preceding the patient’s onset of symptoms or chlamydia diagnosis.; The most recent sex partner should be treated.	Sex partners: current or the most recent must be treated: Cefixime 800 mg as a single dose; If CT has not been excluded, a single dose of doxycycline 100 mg 2 times/day for 7 days must be added.	Contact <90 days before the diagnosis, needs treatment for early syphilis, even if serologic test is negative; Contact >90 days before diagnosis and serological tests are not immediately available, treatment for early syphilis is needed. If serological test is negative treatment is not needed; Partners among populations with high syphilis rates; Long-term sex partners of persons with latent syphilis	Concurrent treatment of all sexual partners is crucial for preventing reinfections.; Partners should abstain from intercourse until they and their sex partners have been treated and any symptoms have resolved.
Highlights	In neonates: An association between oral erythromycin and azithromycin and infantile hypertrophic pyloric stenosis (IHPS) has been reported among infants aged <6 weeks.; IHPS signs and symptoms must be followed-up; Persons treated for chlamydia should be instructed to abstain from sexual intercourse for 7 days after single-dose therapy or until completion of a 7-day regimen and resolution of symptoms if present (Transmission reduction); Patients should abstain from sexual intercourse until all of their sex partners have been treated.; Persons who receive a diagnosis of chlamydia should be tested for HIV, gonorrhea, and syphilis.	In neonates, ceftriaxone must be administered cautiously: In the presence of hyperbilirubinemia (especially premature newborns); If IV calcium is necessary to be administered simultaneously, an appropriate alternative is cefotaxime 100 mg/kg body weight IV or IM, single dose.; In any case and in any age, if chlamydial infection has not been excluded, treatment for chlamydia must be added.	Jarisch-Herxheimer Reaction: acute febrile reaction frequently accompanied by headache, myalgia, and fever within 24 hours after treatment initiation. Antipyretics can be used. DO NOT DELAY TREATMENT BECAUSE OF THE REACTION; In pediatric age, sexual abuse must be investigated in all cases	Recurrent Tv can result from treatment failure, lack of adherence, or reinfection from an untreated sex partner.; Nitroimidazole resistant Tv is concerning due to few alternatives to standard therapy. Metronidazole resistance occurs in 4–10% of cases, and tinidazole apparently around 1%

Table 7.

Treatment for the patient and sexual partners per pathogen with some highlights.

5. Sexual abuse and bacterial sexually transmitted diseases in pediatrics

Sexual abuse should be considered a cause of chlamydial infection among infants and children. Important note: Perinatally transmitted C. trachomatis infection of the nasopharynx, urogenital tract, and rectum can persist for 2–3 years, which is also the most frequent cause of Ng infection in infants and children. If vaginitis is present in preadolescent girls, Ng must be suspected. Nevertheless, pelvic inflammatory disease is less common after vaginal infection in preadolescents. With this finding, Ng must be suspected and tested. Anorectal and pharyngeal infections with Ng in children are frequently asymptomatic; if suspected, samples from these sites must be tested.

Infants and children aged ≥1 month with primary, secondary, or latent syphilis need interdisciplinary treatment including a general pediatrician, a pediatric infectious disease specialist, pediatric psychologist, and social work, which must be evaluated for sexual abuse, and child protective services must be alerted based on local laws.

In the adolescent population, survivors of sexual assault must be examined by experienced clinicians, the obtention of genital or other specimens has to be decided individually and in accordance with local laws. Tv, Ng, and CT are the most common diagnosed pathogens. NAATs for CT and Ng at the site of penetration and for Tv in urine or vaginal specimen are recommended. Empiric antimicrobial regimens must be started, for women must include Ceftriaxone 500 mg IM in a single dose, Doxycycline 100 mg two times per day orally for 7 days and metronidazole 500 mg two times per day orally for 7 days. In men, ceftriaxone and doxycycline are recommended with the same doses than women. For persons weighing ≥150 kg, 1 g of ceftriaxone should be administered.

In children, the most important factors that must lead a clinician to evaluate sexually transmitted diseases due to sexual abuse include evidence of penetration or healed penetrative injury to the genitals, anus, or oropharynx, abuse is reported, the child has a relative or another person in his/her same environment with a sexually transmitted disease, signs or symptoms such as vaginal discharge or pain, genital itching or odor, urinary symptoms, or genital lesions or ulcers.

Conflict of interest

Diana Leticia Coronel Martinez is an employee of Sanofi.