Neonatal conjunctivitis and pneumonia due to C. trachomatis
Neonatal conjunctivitis, often known by its Latin name of Ophthalmia neonatorum, is a conjunctivitis of the eyes of the new born caused by bacterial infection. Usually the infection is derived from the mother's genital tract at birth, in which case the causative organism is either the gonococcus [causative agent of gonorrhoea] or the genital serovars D to K of C. trachomatis. The observation of chlamydial neonatal conjuctivitis which developed three days after a child was born by Caesarian section with intact amniotic membranes suggests the possibility also of a rare transplacental or transmembrane route of infection [Shariat et al., 1992]. Numerous other bacteria may also cause conjunctivitis in the newborn, including commensal Neisseria, pneumococci, Klebsiella pneumoniae and Streptococcus mitis. These latter organisms are probably acquired after birth, as the mode of delivery has little influence [Krohn et al., 1993]. This article is concerned solely with sexually acquired neonatal chlamydial conjunctivitis.
In the developed world, Chlamydia trachomatis is a much commoner cause of sexually acquired neonatal conjunctivitis than the gonococcus, except in certain focal inner city areas. Approximately a third to a half of infants born through a chlamydial infected birth canal will develop neonatal conjunctivitis, the latter figure, from China, probably reflecting the sensitivity of PCR-based methods [Schachter et al., 1986; Shen et al., 1995]. In China, the rate of chlamydial infection of the cervix in pregnant women in one locality was found to be 4.92% while the rate of chlamydial infection of the palpebral conjunctiva in the newborn was 8.57% by direct immuno-fluorescence [Zhang et al., 1994]. These data suggest that chlamydial neonatal conjunctivitis and pneumonia are probably a significant, but little diagnosed problem in the developing world.
Typically, neonatal chlamydial conjunctivitis has an incubation period of 10 - 14 days compared with the much shorter 2 - 3 days incubation for gonococcal ophthalmia. The orbit of the eye is usually quite swollen, and there is a mucoid discharge which is less frankly purulent than that usually seen with overt gonococcal ophthalmia. The infection is particularly common in pre-term babies, who are often born to women at particular risk of C. trachomatis infection [Francois et al., 1989]. It does NOT respond well to treatment with chloramphenicol eye ointment. After some two weeks, a conjunctival swab taken from the eye, smeared onto a microscope slide and stained with Chlamydia trachomatis specific fluorescent monoclonal antibody often shows the presence of an impressively large number of punctate, fluorescing elementary bodies, looking like the "star-spangled sky at night". In neonatal conjunctivitis, the nasopharynx is also commonly infected with C. trachomatis [Beem & Saxon, 1977], presumably via drainage from the oto-lachrymal duct, so it is important to treat the infants with systemic rather than topical antibiotic. As the causative organism is a sexually transmitted infection, it is vital to ensure that the mother and her sexual partner(s) are also treated.
If left untreated, approximately 10 - 20% of infants will develop neonatal pneumonia [Beem & Saxon, 1977], a condition sometimes termed the Beem & Saxon syndrome. C. trachomatis pneumonia acquired at birth is thought to account for some 20 - 30% of all hospitalized pneumonia in infants less than 6 months old [Schachter et al., 1986]. However, most infants do not require hospital treatment.
Occasionally neonatal C. trachomatis pneumonia may be sufficiently severe for the infant to require ventilation [Herieka & Dhar, 2001]. However, typically the onset is insidious, becoming apparent [if it is identified] at some 3 to 12 weeks of age. The infants develop a chronic, staccato, "machine gun-like" cough but are afebrile with minimal malaise but marked chest X-ray changes, and frequently a history of failure to thrive [Beem & Saxon, 1977; Schachter, 1999]. On physical examination the infants tend to have diffuse rales in the chest and are congested and tachypnoeic. Laboratory examination usually reveals hyper-gammaglobulinaemia (particularly IgM) and eosinophilia (>300-400 per mm3). Significant limitations of expiratory airflow have been reported (FEV1, FEV1/FVC, PEF, and FEF 25%-75%), as well as signs of abnormally elevated volumes of trapped air (FRC and RV/TLC ratios). These obstructive patterns were found responsive to isoproterenol inhalation. The obstructive-type pulmonary function tests could not be ascribed to recognized risk factors, such as exposure to smoking at home or a family history of atopy. There were significant long term effects, with abnormal pulmonary function tests persisting seven to eight years after recovery from the acute illness, while a significant number of infected children developed asthma compared to controls [Weiss et al., 1986]. There are marked changes on chest X-ray, although no radiographic findings are specific for C. trachomatis pneumonia. Most chest films show bilateral hyper-expansion and diffuse infiltrates with a variety of radiographic patterns, including interstitial, reticular nodular, atelectasis, coalescence, and bronchopneumonia. Pleural effusion and lobar consolidation are not seen. The radiographic changes generally suggest a more serious illness than that observed clinically [Radkowski et al., 1981].
Infants with untreated chlamydial pneumonia shed C. trachomatis and are symptomatic for many weeks. However soon after commencement of appropriate treatment, such infants cease to shed the organism and generally progress to complete clinical cure [Beem et al., 1979]. Erythromycin and the newer macrolides appear to be relatively effective for interrupting vertical transmission to the baby [Black-Payne et al., 1990] and for treating neonatal conjunctivitis [Hammerschlag et al., 1998]. However, silver nitrate or erythromycin as ocular prophylaxis agents to prevent chlamydial or gonococcal eye infection in the new born have a significant failure rate [Ratelle et al., 1997]. For specific recommendations see: IUSTI treament guidelines and the CDC STI Guidelines 2002. The CDC recommend for chlamydial ophthalmia neonatorum and for chlamydial pneumonia in infants:
- Erythromycin *base or *ethyl succinate *50 mg/kg/day orally divided into four doses daily for 14 days.
NB: Infants treated with erythromycin should be followed for signs and symptoms of infantile hypertrophic pyloric stenosis which has been reported in infants aged <6 weeks who were treated with this drug.
Data on the use of other macrolides ( e.g., azithromycin and clarithromycin) for the treatment of neonatal chlamydial infection are limited although one small study indicates that a short course of azithromycin, 20 mg/kg/day orally, one dose daily for 3 days, may be effective [CDC STI Guidelines 2002].
Laboratory diagnosis of neonatal conjunctivitis and pneumonia
A chlamydial aetiology should be considered in all infants aged less than thirty days with conjunctivitis.
There have been no modern studies of commercial nucleic acid amplification based tests for the diagnosis of neonatal conjunctivitis and pneumonia. Commercial tests are not specifically licensed for use on ocular and nasopharyngeal specimens from neonates. Nevertheless it can be anticipated that these tests should be useful, as C. trachomatis can be identified in nasopharyngeal specimens [or conjunctival swabs] from a high proportion of the infants [Beem & Saxon, 1977]. An alternative in experienced hands is the identification of chlamydial elementary bodies by direct immunofluorescence. Swabs should be collected from the everted eyelid using a dacron-tipped swab or the equivalent recommended by the test kit manufacturer. It is important that specimens contain conjunctival cells, not just exudate! The diagnosis of neonatal C. trachomatis _infection confirms the need for treatment of the mother and her sex partner(s) as well as the infant.
One of the extraordinary features of _C. trachomatis pneumonia in infants is the high number of circulating B cells and plasma cells expressing surface IgM and IgD and cytoplasmic IgM and IgG. These cells secrete exceptionally large amounts of IgM, IgG, and IgA when cultured in the absence of added mitogens. This suggests that C. trachomatis pneumonia induces substantial B-cell activation at a period of human development when antibody responses are normally difficult to stimulate [Levitt et al., 1983]. Not surprisingly, high levels of C. trachomatis IgM antibody (> 1 in 32 in the microimmunofluorescence test) are usually found. This is one of the few instances where the microimmunofluorescence test can be genuinely diagnostically useful. Nevertheless, the possibility of Human_Infections/ChronicDisease.InfectionsChpPneumonia Human_Infections/ChronicDisease.InfectionsChpPneumonia should be considered *and the clinician needs to be aware that, although C. trachomatis pneumonia in neonates has been best studied, other forms of chlamydial respiratory infection do occur and might need to be considered in, for example, the differential diagnosis of bronchiolitis.
[*Comment: Most of the work on neonatal pneumonia was done before there was widespread recognition of the existence and importance of C. pneumoniae as a human respiratory pathogen. There is a need to re-examine the aetiology of pneumonia in neonates and children with new awareness of a possible role for _C. pneumoniae _and perhaps other Chlamydiales.]_*
[MEW] November 2002
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