**2. Gonorrhea**

### **2.1 Epidemiology**

Every year, 87 million new cases of gonorrhea are reported worldwide in the population from 15 to 49 years old (2016 incidence). The median cases rates per 100,000 men from 15 to 49 years old reporting urethral discharge are 82.5 (range: 1.1–6133.7) and gonorrhea are 16.9 (range 0.0–297.1); the highest case rates were reported from the African Region, followed by the European and Western Pacific regions. In the United States, the highest peak of gonorrhea has been reported in the 20–24 years of age (720.9/100,000 in men and 702.6/100,000 in women), the second group of age with the highest incidence is the group from 15 to 19 years old (320.5/100,000 in men and 548.1/100,000 in women) [3]. Latin American countries like Colombia, Peru, and Brazil have been reported an increase in the number of cases in 2000 [4]. The highest prevalence of gonorrhea has been detected in the African Region (1.7%) followed by the Western Pacific Region (around 1.5%) [5]. One of the biggest concerns about gonorrhea is the development of antimicrobial resistance (AMR); in 2016, 57 countries reported that ≥5% of N. gonorrhea (Ng) specimens had decreased susceptibility (including azithromycin and ciprofloxacin) [6].

#### **2.2 The pathogen**

Neisseria gonorrhea (Ng) is a diplococcal gram-negative microorganism and one of the two pathogenic Neisseria species pluralism (spp); this bacterium has 80–90% of similarity to Neisseria meningitidis. Ng genome was sequenced for the first time in 2003. Ng has a high degree of genetic plasticity that enables the rapid evolution of AMR [7].

Ng has evolved mechanisms for evading innate immunity and suppressing adaptive immune responses. Ng prevents complement activation, opsonization, and bacterial killing by binding to complement proteins, sialylating its lipooligosaccharide (LOS) to hide from the complement system. Ng can bind also to the Host factor H and C4b-binding protein (C4BP), becoming serum resistant by presenting as self and by shielding itself from complement recognition [8].

#### **2.3 The disease**

Ng is an obligated human pathogen that is primarily transmitted through genital, oral, and anal sexual contact, infecting mucosal surfaces at these sites leading to the various symptoms associated with gonorrhea. Transmission is highly efficient (a substantial proportion of people become infected after a single exposure); can be asymptomatic or symptomatic (all sites), both can lead to additional Sexual Reproductive Health (SRH) complications (infection itself or inflammatory response); it can be also transmitted to neonates from infected mothers during childbirth infecting the conjunctival mucosa [9].

The asymptomatic infection is frequently unrecognized and is accountable for the larger proportion of all infections, this is the most frequent presentation in women; the acute symptomatic syndrome is the most common presentation in men [8, 9].

#### *Sexually Transmitted Infections in Pediatrics DOI: http://dx.doi.org/10.5772/intechopen.101674*

In women, as already mentioned, most of the infections have no or mild symptoms like vaginal discharge, it is frequently mistaken for other reproductive conditions and the coinfection with Chlamydia trachomatis (CT) is common. In men, gonorrhea is presented as an acute lower genital tract infection with urethritis with purulent discharge or dysuria within 5 days of infection. Among both sexes, extragenital infections of the oropharynx and rectum are usually asymptomatic but can cause symptomatic pharyngitis and proctitis [8, 9].

Ng infections have potential adverse sexual reproductive health outcomes like pelvic inflammatory disease (PID), tubo-ovarian abscesses, infertility, epididymoorchitis, ectopic pregnancy, chronic pelvic pain, urethral stricture in men, and adverse pregnancy outcomes. In the neonate can cause vision loss due by neonatal conjunctivitis. Ng also increases the risk of HIV, finally, the infection can be disseminated (i.e., arthritis, gonococcemia, endocarditis, and meningitis). Ng also generates important psychosocial consequences like stigmatization and negative effects on sexual relationships [7–10].

A recent increase in gonorrhea incidence has been reported, one of the main reasons is the change in sexual behavior in the era of antiretroviral treatment for HIV infection; it seems that people are less cautious and have sex with new and casual partners without condoms [7], this is of particular importance in the adolescent population that is considered a vulnerable group.

Gonorrhea infections are more common in adolescents, followed by neonatal infections; in children between these two periods, sexual abuse should be always considered [10].

## **2.4 Diagnosis**

The most recent definition of a gonorrhea case is the one published by the Centers for Disease Control and Prevention (CDC). This definition includes laboratory criteria for diagnosis and case classification [11]. Observation of Ng in a urethral smear (gram-negative diplococci) from men or an endocervical smear from a female indicates Ng infection; also the isolation by culture can make the diagnosis; finally and more recently, the demonstration of Ng in a clinical specimen by detection of antigen or nucleic acid can also make Gonorrhea diagnosis. A case is confirmed when Ng is isolated by culture or N. gonorrhea is demonstrated in a clinical specimen by detection of antigen or detection of nucleic acid via nucleic acid amplification (e.g., PCR or hybridization with a nucleic acid probe).

For practical purposes, we can consider two types of diagnosis: Clinical gonorrhea defined by a confirmed case and clinical signs and symptoms; and asymptomatic gonorrhea, defined as a confirmed case without clinical signs and symptoms.

#### **2.5 Gonorrhea in children and sexual abuse**

In general, gonococcal infections in children and adolescents can occur in three different age groups [9]:


is mandatory to suspect and manage sexual abuse in the applicable legal and medical context [9, 10].

• In adolescents with active sexual life, in which the infection is often asymptomatic; in female adolescents the Fitz-Hugh-Curtis syndrome and be seen (perihepatitis).

#### **2.6 Treatment**

Since the discovery of the sulfonamides in the 1930's decade followed by Penicillin G, Spectinomycin, 3rd generation cephalosporins, macrolides, and finally fluoroquinolones; Ng has been developed evolutive mechanisms for antimicrobial resistance. The first Ng strain with high-level resistance to ceftriaxone was isolated in 2009 in Japan, same findings occurred in France and Spain 2 years later; other countries like Japan, China, Australia, Singapore, Canada, and Argentina also reported treatment failures with ceftriaxone. In 2014, the first failure of ceftriaxone–azithromycin dual therapy for gonorrhea was verified in the United Kingdom. Since 2015, an international spread of one ceftriaxone-resistant gonococcal strain, initially described in Japan, has been confirmed and the first strain with resistance to ceftriaxone plus high-level azithromycin resistance was isolated in 2018 in the UK and Australia [7–12].

*2.6.1 Uncomplicated gonococcal infections treatment beyond the neonatal period and adolescents*

Considering that older children normally acquire the infection through sexual abuse, it is very important to reduce the traumatic impact of treatment; in these cases, a single dose oral regimen is preferred [10]. The recommended regimens for Ng treatment depend on the location of the infection.

For uncomplicated vulvovaginitis, cervicitis, urethritis, proctitis, or pharyngitis, the primary recommendation is for children who weigh less than 45 kg: ceftriaxone 125 mg IM in a single dose; and for children who weigh 45 kg or more: 250 mg IM in a single dose plus azithromycin, 1 g orally in a single dose. In the case of uncomplicated infections that involve the anal region, dual treatment with cefixime (400 mg orally) and azithromycin may be used if ceftriaxone is not available. For infections located in the pharynx, the primary treatment recommended is ceftriaxone; cefixime should not be used [9, 13]. In the case of cephalosporin allergy, a consultation with a pediatric allergologist or an allergy expert consultation should be performed.

Tests-of-cure are not needed; these are recommended only for pharyngeal locations (test-of-cure 7–14 days after using NAAT or culture).

In the case of persistent infections, other causes must be considered: recurrent Ng infection can be seen among sexually active adolescents previously treated with gonorrhea mostly related to reinfection (i.e., sexual partners did not receive the treatment). It is recommended that this population that has been treated for Ng, should be retested 3 months after treatment [13–15].

#### *2.6.2 Complicated gonococcal infections treatment beyond the neonatal period and adolescents*

Complicated gonococcal infections include arthritis-dermatitis syndrome, meningitis, endocarditis, conjunctivitis, and epididymitis [9, 13–15].

• For disseminated infection, the recommendation is:

	- In children who weigh less than 45 kg: Ceftriaxone (50 mg/kg/day; maximum 2 g/day, intravenous or intramuscular, every 12–24 hours. For meningitis: 10 to 14 days. For Endocarditis: at least 28 days; AND Erythromycin base or ethylsuccinate (50 mg/kg/day; orally divided into 4 doses every day for 14 days.
	- In children who weigh 45 kg or more: Ceftriaxone (1–2 g, intravenous or intramuscular, every 12–24 hours. For meningitis: 10–14 days. For endocarditis: at least 28 days; AND Azithromycin (1 g, orally in a single dose).
	- In children who weigh less than 45 kg: Ceftriaxone 1 g, intramuscular in a single dose.
	- In children who weigh 45 kg or more: Ceftriaxone, 1 g, intramuscular in a single dose; AND Azithromycin 1 g, orally in a single dose.
	- Ceftriaxone, 250 mg intramuscular in a single dose AND doxycycline, 100 mg orally twice daily for 10 days.
