Childhood Chlamydia Infections

Abstract

Chlamydia pneumoniae and Chlamydia trachomatis are significant human pathogens that affect people of all ages worldwide. Chlamydia psittaci is a cause of zoonosis, and birds are the reservoirs. All are diseases for which there is no effective vaccine. C. pneumoniae is responsible for respiratory tract infections but the majority of recent C. pneumoniae research has focused on the persistent infections associated with chronic diseases and has been considered a childhood infection with potential adult consequences. C. trachomatis is one of the most common sexually transmitted diseases (STDs), and the prevalence of the infection is particularly high among young people and adolescents. Prepubertal infection of C. trachomatis may be a warning sign for probable child sexual abuse (CSA). In addition to its role in genital diseases, trachoma is one of the world’s leading preventable causes of blindness. C. trachomatis can also cause Lymphogranuloma venereum (LGV), a systemic, sexually transmitted disease characterized by genital ulceration and inguinal lymphadenopathy. This chapter aims to provide an overview of Chlamydia infections in childhood and summarize the epidemiology, clinical manifestations, and treatment.

1. Introduction

Chlamydia trachomatis and Chlamydia pneumoniae are significant human pathogens that affect people of all ages worldwide. Chlamydia psittaci is a cause of zoonosis, and birds are the reservoirs. All are diseases for which there is no effective vaccine.

All members of the family share a lipopolysaccharide antigen and use host resources to synthesize chlamydial protein. They also encode the major outer membrane protein (MOMP or OmpA), which is surface-exposed in C. trachomatis and C. psittaci but not in C. pneumoniae. The MOMP is the major determinant of C. trachomatis and C. psittaci serologic classification [1, 2].

Chlamydiae are obligate intracellular microorganisms that have a distinct developmental cycle. Understanding this life cycle is important because it underlies the potential problems with laboratory diagnosis, persistent infection, and treatment.

1.1 The biology and life cycle

The chlamydial life cycle is biphasic, with two functional and morphological forms that alternate: infectious “elementary bodies” (EBs) and replicative, non-infectious “reticulate bodies” (RB). The metabolically inactive and infectious “Elementary Body” (EB), which is capable of extracellular survival, binds to the surface of host cells via interactions between bacterial ligands and host receptors, resulting in EB endocytosis. The vesicles containing the EBs are referred to as “inclusion.” Because multiple EBs can bind to and enter the same host cell, multiple inclusions are formed. EBs differentiate into metabolically active RBs after internalization. RBs are specialized in nutrient acquisition and the expression of proteins required for energy synthesis. RBs replicate by binary fission within inclusion bodies, avoid lysosomes by modifying host cell endocytic pathways by changing or mimicking the inclusion membrane, and transform into EBs with the ability to infect new host cells [3]. Host metabolites are used in this process via interactions with multiple host cell organelles. After 48–72 hours, new EBs are released by cell lysis to infect other cells while leaving the host cell alive. In this one-of-a-kind cycle, RBs, the organism’s intracellular form, play a role in disease persistence, while EBs infect new hosts or neighboring host cells [3, 4].

2. Chlamydia pneumonia

Chlamydia pneumoniae was first isolated in 1965 in Taiwan from a child’s eye in a trachoma vaccine study and named TW-183 because it was the 183rd isolate in the laboratory. It was assumed that the isolate was a C. trachomatis serovar, but it was noticed that it did not share any features of C. trachomatis previously tested in laboratory or animal studies. After the micro-immunofluorescence (MIF) serologic test for Chlamydia was developed in 1972, TW-183 remained untypable [5]. These antibody studies concluded that TW-183 was probably not a cause of eye disease but a very common infection. Meanwhile, TW-183 was shown to be the probable cause of a pneumonitis outbreak in Finland [6]. AR-39 was the name of the isolate cultivated from the 39th student’s throat in a university study, with similar characteristics to TW-183 [7]. While “TW-183/AR-39-like organisms” were continuing to be studied in respiratory tract infections, findings suggested that “TWAR” (as a shorthand for typing) strains were most likely a new human C. psittaci strain transmitted from human to human without a bird or animal reservoir [5]. They were shown to be responsible for 12% of pneumonia illnesses and 5% of bronchitis in a university outbreak over a 2.5-year period [5].

In 1989, the TWAR organism was officially announced as “Chlamydia Pneumoniae” as a new species by Grayston, based on distinct morphology, DNA sequence, and clinical disease spectrum in Chlamydiae, 50 years after Joseph E. Smadel first questioned the source of seven “psittacosis cases without known bird contact” [7].

More recently, a new taxonomic classification was proposed after genome sequencing, in which the genus Chlamydia pneumoniae would be replaced with a new genus name, Chlamydophila pneumoniae [8, 9]. Since the genus Chlamydophila would be composed of most veterinary chlamydiae and the proposal was not universally accepted, especially by the clinicians, and since both names are currently in use by different authors, the former, more widely recognized designation (Chlamydia pneumoniae), will be used in this review and will refer to Chlamydophila pneumoniae, biovar TWAR.

Even though C. pneumoniae is a common pathogen responsible for respiratory tract infections, the majority of recent C. pneumoniae research has focused on the pathogen’s role as a cause of persistent infections in human chronic diseases and is considered a childhood infection with adult consequences. C. pneumoniae has been linked to a wide range of diseases, including cardiovascular disease, Alzheimer’s disease, arthritis, ischaemic stroke, asthma, and lung cancer [10].

2.1 Pathogenesis

Chlamydia pneumonia appears to enter the human body via the respiratory mucosal epithelium, and it has been shown that, after infecting lung epithelial cells and alveolar macrophages, they can infiltrate different cell types such as monocytes, macrophages, monocyte-derived dendritic cells (DCs), lymphocytes, and neutrophils [10]. When C. pneumonia is not eradicated, RBs, keen on hiding from the host immune system within inclusion bodies, can persist intracellularly for long periods of time and cause chronic infection. Chronically infected monocytes can spread all over the body via the lower respiratory tract after intranasal CP inoculation in mice [11].

2.2 Epidemiology

The mode of transmission of the bacteria in children is not well understood, but it is thought to be similar to other respiratory infections, and transmission occurs from human to human through infected respiratory tract secretions.

It is challenging to describe the epidemiology of C. pneumonia precisely. The studies published after the initial identification, during the 1990s, defined the organism as being associated with 6–22% of lower respiratory tract infections in children and adults [12, 13, 14, 15]. After the consideration of C. pneumoniae’s long-term effects, studies continued with an acceleration number in various populations, with different and more sensitive diagnostic methods. Heterogeneity in the serological methods and study population (hospitalized/outpatient, ages, used criteria in the diagnosis) makes it difficult to compare the results.

Serological studies showed that C. pneumoniae is common, with a seroprevalence of over 50% among adults, indicating previous infection [16, 17, 18, 19]. In addition, prevalence is relatively low in children under five to ten years (7–8%), sharply increases by the age of 20 (%40–55), and continues to increase gradually to rise in the elderly to 70–80% [16, 20].

C. pneumoniae is considered to affect mostly school-aged children, and initial infection time peaks between 5 and 15 years of age; however, with expanding knowledge, this statement may alter as well. Some studies have shown that the prevalence rate of infection in younger children may be similar to that in older ones. A population-based seroepidemiological survey of students from Italy showed that 23% of the first graders had early exposure to C. pneumoniae infection in the community [21]. It seems that the age of primary infection due to C. pneumonia seems to differ due to the diagnostic test used. Most young children are not able to develop specific antibodies when culture or PCR testing is used. Colonization or possible infection in younger children would also be identified in the absence of a detectable antibody response.

There is no evidence of seasonality. The mean incubation period is 21 days.

2.3 Clinical presentation

Chlamydia pneumoniae infection is frequently asymptomatic or manifests with mild symptoms. C. pneumonia, infecting the upper respiratory epithelium in children, can cause or contribute to acute otitis media and sinusitis, as well as protracted cough illnesses and community-acquired pneumonia.

Upper respiratory tract infections caused by C. pneumoniae actually do not have a distinctive clinical picture, and patients may be asymptomatic, mildly, or moderately ill, with non-specific respiratory complaints. In general, signs and symptoms of respiratory infections have little value in the diagnosis of C. pneumoniae.

Clinical manifestations of the C. pneumoniae infection as upper respiratory tract infections were established as pharyngitis, otitis, and sinusitis, with an incidence of 5–10% in the initial studies [7, 22]. Nasopharyngitis (46%) was the most common clinical presentation in school-aged respiratory infections related to C. pneumoniae, documented by PCR positivity [23]. In a recent study, C. pneumoniae was detected by PCR in 38% of children under 10 years diagnosed with an upper respiratory infection in Brazil [24].

“Sore throat” and “hoarseness” are particular symptoms commonly mentioned in the studies in which either the upper or lower respiratory tract was included [22, 23]. Although fever and related respiratory symptoms can be self-limited, the cough usually follows pharyngitis. The clinical progress can be biphasic and end up in atypical pneumonia. The infection is often associated with a persistent cough when the lower respiratory tract is included. C. pneumoniae was isolated in 17% of the infants with prolonged coughing [25]. The mean duration of cough associated with a C. pneumoniae infection has been reported as 25–30 days.

Clinical features of C. pneumoniae pneumonia are similar to those of other community-acquired pneumonia (CAP), including fever, cough, tachypnea, and shortness of breath. Physical examination may reveal nonexudative pharyngitis, pulmonary rales, and bronchospasm. It is not feasible to distinguish the causative agent according to clinical or routine laboratory tests [26, 27]. Chest radiograph findings generally are nonspecific and include patchy subsegmental infiltration, bilateral infiltrates, segmental and lobar consolidation, and even pleural effusion [27, 28, 29, 30].

Data gained from the epidemics painted a clinical picture of mild but long-lasting pneumonia in previously healthy young adults [6]. With our expanding knowledge, it seems that the course of the disease may vary with the patient’s age, the presence of co-pathogens, or the existence of comorbidities. Severe and life-threatening infections have been reported [31]. Coinfection with other pathogens is possible and may affect clinical presentation [32].

C. pneumoniae can manifest as severe community-acquired pneumonia in immunocompromised hosts and has been associated with the onset or acute exacerbation of respiratory symptoms in patients with asthma, cystic fibrosis, and acute chest syndrome in children with sickle cell disease; rare cases of meningoencephalitis and myocarditis have also been attributed to the pathogen [33].

2.4 Diagnosis

The micro immunofluorescent (MIF) antibody test is the most sensitive and specific serologic test for acute infections, but it cannot be used to make an instant diagnosis. A fourfold increase in IgG levels in acute and convalescent sera is diagnostic. IgM titers greater than 1:16 are indicative of acute infection. IgM increases 1–2 weeks after the onset of primary infection, but not upon reinfection. It should be considered that early antibiotic treatment may suppress the antibody response.

NAATs, such as real-time polymerase chain reaction (PCR) assays, can detect the organism on nasopharyngeal swabs, bronchoalveolar lavages, and sputum samples with high sensitivity and specificity and are useful for rapid and accurate diagnosis [33]. C. pneumoniae can be isolated from swab specimens, sputum, bronchoalveolar lavage, and tissue biopsy specimens, but the organism is relatively hard to culture.

2.5 Treatment

Chlamydia pneumoniae appears sensitive to tetracyclines, macrolides, ketolides, and the majority of fluoroquinolones (e.g., levofloxacin and moxifloxacin but not ciprofloxacin). A total of 70–90% of children with C. pneumoniae pneumonia eradicate the organism from the nasopharynx after a 10-day course of erythromycin, clarithromycin, or a 5-day course of azithromycin [26, 34, 35]. When tetracycline or doxycycline is prescribed, typical treatment regimens consist of 14–21 days: 14 days for erythromycin, 7–14 days for fluoroquinolones or clarithromycin, and 5 days for azithromycin.

Clinical improvement occurs in a high proportion of children even if they are untreated or given beta-lactam antibiotics which are thought to be ineffective [36]. On the other hand, despite 10–30 days of appropriate treatment, ongoing isolation of the organism persists in some patients [37].

3. Chlamydia Trachomatis

C. trachomatis is the most prevalent sexually transmitted bacterium in the world [38]. It is a significant public health concern [39].

Although chlamydia typically affects sexually active adolescents or adults, this infection can also be transmitted vertically during delivery from their infected mothers.

Prepubertal infection of C. trachomatis may be a sign of probable child sexual abuse (CSA), necessitating a multidisciplinary thorough investigation.

In addition to its role in genital diseases and associated perinatal infections, trachoma is one of the world’s leading preventable causes of blindness. C. trachomatis can also cause Lymphogranuloma venereum (LGV), a systemic, sexually transmitted disease characterized by genital ulceration and inguinal lymphadenopathy.

3.1 Classification

C. trachomatis encodes an abundant surface-exposed protein known as the major outer membrane protein (MOMP or OmpA), which is the primary determinant of serologic classification. Based on antigenic variation in the major OMPs (serovars) and clinical expression, C. trachomatis is subdivided into subgroups. Microimmunofluorescence and monoclonal antibody testing have revealed that there are over 18 serovars of C. trachomatis classified under three biovars [4].

In developing nations, the trachoma biovar (serovars A–C) is the leading cause of non-congenital blindness, whereas the genital tract biovar (serovars D–K) is the most common sexually transmitted bacterium, each of which is associated with a distinct clinical presentation [1, 3] Serovars A, B, Ba, and C cause trachoma; serovars B, Da, Ga, Ia, and D-K cause oculogenital and neonatal disease; and serovars L1, L2, L2a, and L3 cause lymphogranuloma venereum (LGV).

3.2 Pathogenesis

The major symptoms of C. trachomatis infection are not due to direct pathogen activity but rather to the host’s immune response to infection. LGV serovars can proliferate in lymph nodes and macrophages, whereas other types of C. trachomatis can only replicate in mucosal epithelial cells. After 7–21 days (on average, 10 days), various clinical symptoms manifest due to tissue degradation or the host’s inflammatory response. Neutrophil infiltration distinguishes the initial stages of the primary infection. Although lymphocytes and plasma cells contribute to the initial response, they also play a role in the resolution of the infection [40, 41]. Plasma cells predominate in ocular and genital tract infections [42, 43], whereas eosinophils and neutrophils predominate in neonatal pneumonia [44]. Chlamydial infections can be self-limiting and asymptomatic or infections can be persistent for months or years, it is assumed that the host will develop some form of a protective immune response [45, 46, 47]. However, natural C. trachomatis infection is insufficient to prevent reinfection. Since the majority of chlamydial infections of the genital tract are asymptomatic, the risk of chronic, untreated infections is high.

3.3 Epidemiology

Different strains of C. trachomatis infect either the mucosa of the genital tract or the eye. In endemic regions, primarily in Africa and the Middle East, C. trachomatis causes trachoma, the leading preventable cause of blindness globally. Approximately 136 million people reside in trachoma-endemic areas in 44 countries [48].

C. trachomatis is the most common bacterial cause of sexually transmitted infections (STIs) worldwide. According to the World Health Organization’s (WHO) global surveillance of STIs in 2018, the global estimate of new CT cases in 2016 was 127 million [49]. Genital Chlamydia infections are asymptomatic in 61% of women and 68% of men; consequently, they are frequently misdiagnosed and untreated, resulting in transmission to others.

The most strongly associated sociodemographic factor with chlamydial infection is young age (<20 years). C. trachomatis was found in 6.5% of high school students, with rates among girls being more than double those of boys (4.0% versus 9.7%), and rates of infection increased with age [50]. In a study of over 3000 sexually active middle-school-aged female adolescents, 29% of them had at least 1 positive test result, and the highest age-specific prevalence rate (28%) was found in 14-year-old females [51]. The prevalence of CT infection was 11.5% among adolescents and 6.2% among young adult women.

3.4 Clinical presentations of C. trachomatis in children

C. trachomatis infects non-ciliated squamocolumnar or transitional epithelial cells that are susceptible (e.g., mucous membranes of the conjunctivae, posterior nasopharynx, urethra, endocervix, and rectum).

3.4.1 Perinatal infection

Typically, a newborn acquires an infection while passing through an infected birth canal, but it is known that transmission via cesarean delivery is possible, whether or not the membranes rupture prematurely. The prevalence of C. trachomatis infection in pregnant women varies depending on the population studied, ranging from 2 to 20% [52, 53, 54]. As in the general population, young women, particularly adolescents, had the highest prevalence of infection during pregnancy. In a British study of 1216 pregnant women, the overall CT infection prevalence was 2.4%, but it increased to 8.6% under the age of 25 years and 14.3% in the adolescent group [55]. Another study found that 18% of 203 pregnant adolescents had C. trachomatis infection in the third trimester of pregnancy [56].

The conclusion of many studies done in the 1980s was that maternal carriage of C. trachomatis is associated with a high incidence of clinical illness in infants. Prospective studies of infants born to mothers with chlamydial infection of the cervix have revealed a 50–75% risk of C. trachomatis acquisition in at least one anatomic site, including the conjunctiva, nasopharynx, rectum, and vagina [57]. Infants exposed to untreated C. trachomatis are estimated to have a 20–50% risk of conjunctivitis and a 5–20% risk of pneumonia [57, 58, 59]. In a recent Chinese study, the vertical transmission rate was determined to be 67% after vaginal delivery and 8% after a cesarean section [60]. Symptomatic chlamydia appears in infants mostly between the ages of 4 and 5 weeks, with a range of 2–20 weeks [56, 61].

3.4.1.1 Inclusion conjunctivitis

C. trachomatis has been reported to be the most prevalent cause of ophthalmia neonatorum in many countries and neonatal conjunctivitis is the primary clinical manifestation of chlamydial infection in neonates [62, 63, 64]. The findings of studies conducted in various countries clearly show that the distribution of key etiological agents of newborn conjunctivitis corresponds to the real prevalence of STI infections among pregnant women.

Ocular findings start usually between 5 and 14 days postpartum, although they can occur earlier if a premature membrane rupture is present. Mucopurulent discharge (95%), swelling of the eyelids (73%), and conjunctival erythema (65%) are the defined symptoms [65]. The vast majority of cases resolve spontaneously, but conjunctivitis can be long-lasting and severe; in the condition of severe inflammation, a pseudomembrane formation develops as a result of large exudates adhering to the conjunctivae. Conjunctivae may bleed during the examination or sampling. Corneal ulceration, scarring, and pannus formation are uncommon; and recovery without visual impairment is expected. Bloodstained eye discharge was found to have high specificity and positive predictive value for chlamydial conjunctivitis in a retrospective study of 90 infants from Hong Kong with chlamydial conjunctivitis [66]. At least 50% of infants with chlamydial conjunctivitis also have a nasopharyngeal infection, and 50% of the pneumonia cases have evidence of previous conjunctivitis [56, 67].

Neonatal prophylaxis with antibiotic-containing ointments has no effect on the incidence of chlamydial conjunctivitis or the development of nasopharyngeal carriage and pneumonia [68, 69].

Differential diagnosis of gonococcal and other pyogenic conjunctivitis is not possible based on clinical findings, but ophthalmia neonatorum due to gonococcal infection usually begins earlier (postnatal 3–5 days).

3.4.1.2 Neonatal pneumonia

The importance of C trachomatis as a causal pathogen for respiratory illness in young infants is well documented in the literature [62]. C. trachomatis seems the etiological agent of 7–30% of the hospitalized pneumonia cases before 6 months of age [70, 71, 72, 73, 74].

Clinical manifestations of chlamydial pneumonia typically appear between the ages of 3 and 12 weeks. The majority of the infants are only mildly ill and afebrile. Nasal obstruction and staccato cough worsen over one or more weeks. Tachypnea and rallies are found on physical examination, but wheezing is uncommon. An X-ray of the chest will usually show hyper aeration as well as bilateral interstitial infiltration. Peripheral eosinophilia (>400 cells/mm³) is a distinctive laboratory finding but the total white cell number is usually normal [73, 75]. Concomitant or history of conjunctivitis is present in 30–50% of cases. The absence of fever and significant wheezing may be useful in the differential diagnosis of RSV infection, which is the most common pathogen in this age group.

Infected preterm neonates, may present differently. They can be symptomatic as early as 48 hours after birth, manifesting as idiopathic respiratory distress syndrome, which improved initially but was complicated by apneic spells and feeding difficulties [76]. Severe infections causing respiratory failure are also defined in the literature [77, 78, 79].

3.4.1.3 Infections at other sites

It is possible to detect asymptomatic rectal or vaginal C. trachomatis in 14% of neonates born to women with chlamydial infection, which can persist for 18 months [80, 81]. The presence of C. trachomatis in the genital tract can complicate the evaluation of probable sexual abuse and necessitates a thorough investigation [81].

3.4.2 Infections in older children

No specific clinical syndrome has been associated with C. trachomatis in older infants and children. The majority of focus on C. trachomatis infection in these children has centered on its association with child sexual abuse. As mentioned previously, perinatal maternal–infant transmission resulting in vaginal and/or rectal infection has been documented with up to three years of prolonged infection.

If C. trachomatis established in a prepubertal child from a rectal or genital site, sexual abuse must always be considered and a detailed multidisciplinary assessment of sexual abuse should be performed [82]. There is no evidence in the literature about the transmission of this organism without sexual activity such as via fomites.

3.4.3 Infections in adolescents

3.4.3.1 Oculogenital infections

Half of the approximately 20 million new sexually transmitted infections (STIs) diagnosed annually in the USA affect those aged 15–24 and both male and female STI rates are on the rise, with the majority of this increase occurring among adolescents [83]. It is estimated that one in four sexually active adolescent girls have a sexually transmitted infection, most commonly C. trachomatis (CT) and human papillomavirus (HPV) [84].

From a behavioral and biological point of view, adolescents are presumed to engage in high-risk sexual behavior, such as having multiple partners or not using a condom. And due to the biological factors, it is known that adolescent females are susceptible to sexually transmitted diseases due to cervical ectopy, and lower production of cervical mucous. Studies indicate that C. trachomatis infection is more prevalent in patients with cervical ectopy, which is more common in adolescents [85, 86]. In addition, most C. trachomatis infection is asymptomatic and adolescents are less likely than adults to apply for sexual health services and have STD screening. Healthcare professionals usually do not feel confident about questioning adolescents and young adults about their sexual behaviors, assessing for STI risks, and screening for STIs. These factors contribute to creating an ongoing reservoir for infection and a lower chance of diagnosis and treatment.

Females infected with Chlamydia may develop cervicitis, urethritis, and proctitis, and males may exhibit urethritis, proctitis, and epididymitis as manifestations. In the majority of cases, heterosexual transmission accounts for a high rate. Since the majority of chlamydia infections, including non-genital infections, are asymptomatic, routine screening of at-risk populations is recommended for preventing transmission to sexual partners and preventing complications of untreated infections. A total of 82 Colombian women were followed for five years using serotyping and polymerase chain reaction (PCR) on cervical-scrap samples; it was stated that untreated, approximately 46% of infections were persistent at one year, 18% at two years, and 6% at four years, and manifesting symptoms were dysuria/pyuria syndrome, vaginal discharge, intermittent bleeding, and moderate abdominal pain [47]. Besides, they noticed that C. trachomatis can cause vaginitis in adolescence but not in adults; the squamous epithelium of the adult vagina is not vulnerable, and vaginal discharge is generally indicative of endocervical infection.

In women who do not get treatment, an ascending acute urogenital infection can cause severe, long-lasting pelvic inflammation. This can show up as endometritis, salpingitis, PID, chronic pelvic pain, etc., and it can damage the tubes, which can lead to infertility and ectopic pregnancy. The spectrum of PID associated with C. trachomatis infection extends from asymptomatic to a severe, acute disease characterized by perihepatitis and ascites (Fitz-Hugh–Curtis syndrome). It has been discovered that chlamydia screening reduces the incidence of PID [87].

In the USA, a national cross-sectional prospective cohort found that 95% of C. trachomatis-infected people had no symptoms. The most common symptoms among infected males were urethral discharge (3%) and dysuria (2%), while the most common symptoms among infected females were vaginal discharge (0.3%) and dysuria (4%). And seropositivity was only in 1% of vaginal discharges [88, 89]. A total of 38% of males reporting urethral discharge and 6% of females reporting dysuria were found to be positive for C. trachomatis.

Epididymitis, reactive arthritis (including Reiter syndrome), and transmission to females are the primary complications of chlamydial urethritis in men.

Although asymptomatic rectal and nasopharyngeal carriage of C. trachomatis can occur in both infants and adults, C. trachomatis is also reported as a cause of proctitis [90, 91].

Inclusion conjunctivitis is an extra-genital manifestation of this STD in both sexes that results from oto-inoculation of the eyes with contaminated genital secretion, typically as acute follicular conjunctivitis. The symptoms are usually a sensation of a foreign body in the eye. In most cases, the infection resolves without complications; however, if left untreated, it can persist for months and cause damage.

3.4.3.2 Lymphogranuloma Venereum

LGV is a STI caused by the L1 to L3 C. trachomatis serovars.

The bubonic form of the disease is endemic to tropical and subtropical regions. Classically, LGV starts with a small papule or ulcer and days to weeks after the primary lesion resolves spontaneously, unilateral inguinal lymphadenitis, and hemorrhagic proctitis develop. Systemic symptoms may accompany it, including fever, myalgia, and headache. Approximately one-third of inguinal buboes drain, and the rest involute slowly. Due to the persistence of chlamydia in anogenital tissues, a small proportion of patients with LGV develop a chronic inflammatory response with fibrosis, which can lead to chronic genital ulcers or fistulas, rectal strictures, or genital elephantiasis.

3.4.4 Trachoma

Trachoma remains one of the world’s primary causes of blindness; approximately 30% of children in a holoendemic region are at risk of blindness due to severe trachoma [47]. Both pannus formation and progressive disease with scarring are thought to be the result of a long-term cycle of active infection and healing over the years.

In areas where trachoma is endemic, infections occur early in life and the disease remains active for several years. Poor hygiene and the presence of eye-seeking insects increase the likelihood of transmission. Inclusion conjunctivitis’ characteristic chronic follicular conjunctivitis first appears, then the conjunctivae become more intensely inflamed, and finally, the tarsal conjunctiva fibrosis occurs. Trichiasis (turning of the eyelashes) frequently develops following extensive scarring of the inner surface of the lids. This causes additional corneal ulceration, fibrosis, opacification, and vision loss. Young adolescents with active trachoma can have C. trachomatis isolated from conjunctival scrapings and nasopharyngeal cultures.

3.5 Diagnosis

NAATs such as PCR assays are the guideline-recommended method for pathogen identification in acute urethritis [92]. First-catch urine or a urethral swab specimen can be used. NAATs also have more sensitivity and specificity than culture in nasopharyngeal and rectal infections both in males and females [93, 94, 95, 96]. For urogenital infections in females, NAATs are the most sensitive tests as well and are recommended for laboratory diagnosis.

Both cell culture and nonculture assays are sensitive and specific diagnostic techniques such as direct fluorescent antibody tests (DFA) and NAAT, in the diagnosis of neonatal chlamydial conjunctivitis [97, 98]. Because eye discharge alone is not sufficient, conjunctival cells are required, and the specimen should be obtained from the everted eyelid using a dacron-tipped swab.

For chlamydial infant pneumonia, cell culture is the definitive standard diagnostic test. Specimens collected from the posterior nasopharynx are recommended or tracheal aspirates and lung biopsy specimens if collected. Chlamydia culture in tissue culture is a sensitive and specific method for detecting neonatal chlamydial infections; however, it is time-consuming and costly and has been largely replaced by NAATs. DFA or NAATs can be used in the same specimens but have lower sensitivity and specificity than culture. Microimmunofluorescent (MIF) serum titer of C trachomatis-specific immunoglobulin Ig M > 1:32 is diagnostic.

Only molecular testing that is specific to LGV can provide a definitive diagnosis of LGV (for example, PCR-based genotyping).

Trachoma of the eye is typically diagnosed clinically in countries where the disease is endemic.

When concerning possible sexual child abuse, it is preferred the child be referred for complete evaluation and management to an experienced/specialized pediatrician, clinic, or child advocacy center, with a prompt examination for other SDIs as well. If sexual abuse is suspected, appropriate social service and law enforcement agencies must be contacted to evaluate the situation, ensure the child or adolescent’s safety, and provide appropriate counseling.

3.6 Treatment

Because the elementary body is metabolically inactive, the treatment should target the intracellular form of the organism and have strong intracellular penetration. And, given CT’s 36–48-hour intracellular formation cycle, a long therapeutic duration or a long half-life antibiotic should be chosen to assure appropriate levels of the antibiotic.

To prevent C. trachomatis infection-related complications, decrease the risk of transmission to sex partners and newborns in pregnant individuals, resolve the symptoms, eradicate the microorganism, and prevent re-infection, screening and treating adolescents and young people are recommended. After starting doxycycline or azithromycin, clinical improvement is achieved in 83–86% of symptomatic patients with cervicitis and urethritis [98]. By the way, because most of the patients are asymptomatic, microbial eradication should be targeted.

Inclusion conjunctivitis or Pneumonia of infancy: Erythromycin (50 mg/kg/day in 4 doses) for 10–14 days or Azithromycin (10 mg/kg/day) for 5 days [33]. Empiric antibiotic treatment is recommended for neonatal pneumonia till to diagnostic results are available, but not for conjunctivitis [98].

Genital infections in adolescents: CT is shown to be susceptible to tetracyclines, macrolides, and some of fluoroquinolones [99]. Although amoxicillin is effective, penicillins are accused of easing the in vitro persistence of the microorganism [100].

If laboratory diagnosis is not possible, symptomatic patients with cervicitis, urethritis, epidydymithis, or acute prostatitis who have had recent known or possible sexual exposure can be offered empiric treatment for CT.

Doxycycline is given as 100 mg twice daily for seven days, or single-dose 1 gram azithromycin is recommended by the CDC in the treatment of genital chlamydia infections [83].

Although doxycycline seems microbiologically more effective than azitromycin, especially in rectal infections [101, 102, 103], azitromycin has the advantage of better adherence to treatment with a single dose. Levofloxacin and ofloxacin are the alternative antibiotics recommended.

4. Chlamydia psittachi infections

Chlamydophila psittaci can cause systemic infection and pneumonia, often called psittacosis or ornithosis The pathogen Chlamydophila psittaci can cause systemic infections and pneumonia, often called psittacosis or ornithosis. Previously, it was classified under the genus of Chlamydia but now it is grouped with C. pneumoniae and some other veterinary species in the genus Chlamydophila of the family Chlamydiaceae [4].

4.1 Epidemiology

Psittacosis is responsible for 1% of incident cases of CAP, according to a recent meta-analysis [104]. From 1990 to 2008, the Centers for Disease Control and Prevention (CDC) received 756 reports of psittacosis, of which 9% involved individuals younger than 20 years old [105]. It is not a well-recognized disease by clinicians, there are difficulties in the diagnosis of infection and may be due to underreporting, it is thought that this may not be reflecting the actual number of cases. It is not a well-recognized disease by clinicians, there are difficulties in diagnosing infection, and because of underreporting, this may not reflect the actual number of cases.

C. psittaci is transmitted through the inhalation of aerosols containing respiratory tract secretions, eye secretions, urine, or feces from infected birds. Even limited exposure to infected birds or their droppings can cause illness. Most reported cases of psittacosis have been linked to exposure to domestic birds. Since C. psittaci is resistant to drying and can remain infectious for months in the environment, avian exposure may not be reported in some cases.

4.2 Clinical manifestations

Psittacosis classically causes “atypical” pneumonia. Disease presentations can range from minor influenza-like symptoms to severe systemic diseases. The incubation period is typically between 5 and 14 days, but symptoms can appear up to one month after exposure. It is impossible to make a differential diagnosis according to clinical features compared to other pathogens of community-acquired pneumonia [106]. Psittacosis should be considered in any child with pneumonia who has had close contact with birds.

4.3 Diagnosis

Historically, the diagnosis of C. psittaci disease was based on clinical presentation and a positive microimmunofluorescence (MIF) with paired sera serologic test results. Despite the fact that the MIF test is generally more sensitive and specific than complement fixation (CF) assays, MIF still exhibits cross-reactivity with other Chlamydia species in some cases. NAATs and PCR tests are currently accessible only in specialized laboratories [107].

4.4 Treatment

Doxycycline, erythromycin, and azithromycin are the drugs recommended for treatment.