These policy guidelines for the prevention and control o f Chlamydia trachomatis infections were established after careful deliberation by a group of experts# and sta ff of the Centers for Disease Control (CDC) .' Commentary received after preliminary documents were circulated among a large group o f physicians was also considered Certain aspects o f these guidelines represent the best judgment o f experts. The guidelines should not be construed as rules, but rather as a source o f guidance within the United States. This is particularly true for topics that are based on limited data.# Background
Infections caused by Chlamydia trachomatis are now recognized as the most prevalent-and are among the most damaging -of all sexually transmitted diseases (STD) seen in the United States today (/). An estimated 3-4 million Americans suffer from a chlamydial infection each year (2). Men, women, and infants are affected, but women bear an inordinate burden because of their increased risk for adverse reproductive consequences. While C. trachomatis infection is currently not a reportable disease on a national level in the United States, data obtained from metropolitan STD clinics suggest sharp increases in inci dence in the period 1975-1983 (/). In England and Wales, where nongonococcal urethritis (about half the cases of which are caused by C. trachomatis) is a reportable disease, the inci dence has nearly doubled in the last decade ( 1).
Chlamydiae are unique microorganisms whose specific properties have been delineated largely in the last tw o decades. Although they are classified as bacteria, they share properties with viruses and bacteria. Like viruses, chlamydiae grow only intracellularly. For this reason, culture of Chlamydia has been difficult because expensive cell-culture methods similar to those used to recover viruses are required. Unlike viruses, however, chlamydiae contain both deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), divide by binary fission, and have cell walls similar to those of gram-negative bacteria.
The wider availability of laboratory diagnostic tests for Chlamydia has opened the door to further exploration of the broad spectrum of disease caused by this organism C. trachomatis is now recognized as the causative agent for a diverse group of genital and neonatal infections, including many that were previously considered to be of unknown cause ( 1,3,4) (Table 1).
C. trachomatis causes approximately 50% of the reported cases of nongonococcal urethri tis (NGU) among men. This STD has an estimated incidence 2.5 times that of gonococcal urethritis ( 1 ). Chlamydia is also responsible for approximately 50% of the estimated 500,000 cases of acute epididymitis seen each year in the United States (2)
Even more important are chlamydial infections among women. Most of these infections are asymptomatic, but C. trachomatis also plays an important role in causing mucopurulent cervicitis (MPC) (5), acute pelvic inflammatory disease (PID) (6), and maternal and infant in fections during pregnancy and following delivery (7). Chlamydia accounts fo r one-quarter to one-half of the 1 million recognized cases of PID in the United States each year. These infec tions, in addition to C. trachomatis infections of the fallopian tube not clinically recognized as PID, contribute significantly to the increasing number of women who experience ectopic pregnancy or involuntary infertility. Besides its association with mucopurulent cervicitis and PID, Chlamydia plays an important role in the urethral syndrome (dysuria-pyuria syndrome) and in perihepatitis or Fitz-Hugh-Curtis syndrome ( 1,8).
Maternal infection during pregnancy has been associated with postpartum endometritis and in some studies with an increased perinatal mortality; the latter relationship requires fur ther study. Infants with infected mothers can acquire a chlamydial infection at birth from con tact with infected cervicovaginal secretions. Each year more than 155,000 infants are born to Chlamydia-infected mothers. These newborns are at high risk of developing inclusion con junctivitis and pneumonia and are at slightly elevated risk of having otitis media and bronchi olitis. In fact, Chlamydia is the most common cause of neonatal eye infections and of afebrile interstitial pneumonia in infants < 6 months of age.
Enormous cost is associated with chlamydial infections. Each year, more than $1 billion in direct and indirect costs are expended on these infections in the United States. Many of these Trachoma, the leading cause of preventable blindness in the world, is also caused by C h la m y d ia but has been excluded because it is not generally sexually transmitted, tA rrow indicates direction of transmission of infection.
Question mark indicates that a relationship has not been firm ly established.
Associated with lymphogranuloma venereum. costs result from the management of women with PID and its complications (9) and from the management of infants hospitalized with chlamydial pneumonia. This estimated cost does not reflect the human suffering experienced by those with chlamydial disease. Further growth in the economic burden of chlamydial infections will occur as these infections become more prevalent.
To reduce the morbidity and subsequent complications associated with C. trachomatis in fection in the United States, effective prevention and control strategies must be implemented. Comprehensive guidelines for the formulation of such control programs, as well as diagnostic and therapeutic approaches to infected individuals, are provided in this document. These policy guidelines were established after careful deliberation by an invited panel of experts in collaboration with staff of the Division of Sexually Transmitted Diseases, CDC.

# R isk A s s e s s m e n t
Establishing a profile fo r patients at increased risk of having a genital infection caused by C. trachomatis can be based on multiple criteria.

# Individual Characteristics and Practices
Age, number of sex partners, socioeconomic status, and sexual preference are predictors of C. trachomatis infection. Genital infection rates appear to be inversely related to age and posi tively correlated with number of sex partners. Sexually active women < 20 years of age have chlamydial infection rates 2-3 times higher than those for women ^ 20 years of age, and the rates for women ages 20-29 are considerably higher than those for women ^ 30 years of age (/, 10). Similarly, the rates of urethral infection among teenage males are higher than those for adults (11). Risk of infection increases with the number of sex partners (12,13).
In some studies, lower socioeconomic status and ethnicity have been correlated with an i creased risk of chlamydial infections (10-12). The prevalence of urethral chlamyd.al .nfect.on among homosexual men is approximately one-third the prevalence among heterosexual men (11,14), but 4%-8% of homosexual men seen in STD clinics have rectal chlamydial infection.

# Clinical Syndromes
Several clinical syndromes are associated with C. trachomatis infection. Some are more clearly defined than others, and their prevalence and manifestations differ depending on the population studied. Nevertheless, these conditions often provide the most suitable basis for initiating treatment, especially if complete bacteriologic evaluation is not possible or while the practitioner awaits the results of specific laboratory tests. However, it cannot be overempha sized that most women with cervical chlamydial infection, most homosexual men with rectal chlamydial infection, and as many as 30% of heterosexual men with chlamydial urethritis have few or no symptoms. These asymptomatic infections can sometimes be recognized by physical examination or by increased numbers of leukocytes on a Gram stain of infected secretions.
Three Chlamydia-associated syndromes- are common among women: (1) MPC, (2) ureth ral syndrome or urethritis, and (3) PID. C. trachomatis has been isolated from 30% to 50% of women examined who have mucopurulent endocervical exudate (5). Similarly, C. trachomatis *For a m ore com plete description o f syndromes, see section on Treatment Regimens, pages 65S-67S.

# 56S MM W R
A u g u st 23,1985 has been isolated from female patients with acute dysuria, particularly those with pyuria and a negative Gram stain of unspun urine (8). Among women with PID, the Chlamydia recovery rate is approximately 25%-50% with optimal technique, but serologic data suggest that as many as 50% of acute PID cases may be associated with C. trachomatis. Two Ch/amydia-assoc\aXe6 syndromes are common among men: nongonococcal urethritis (NGU) and acute epididymo-orchitis. C. trachomatis has been consistently isolated from up to 50% of men with NGU. Likewise, investigators have cultured C. trachomatis from 30% to 50% of patients with acute epididymitis and have demonstrated the organism to be the lead ing known cause of epididymitis among men < 35 years of age ( 1 ).

# Contact with an STD Patient
Individuals with a history of sexual exposure to persons with a chlamydial or gonococcal infection are themselves at high risk for chlamydial infection. Approximately 70% and 36%, re spectively, of female sex partners of men with confirmed chlamydial urethritis or confirmed gonococcal urethritis have Chlamydia isolated from the endocervical tract. Of all the women whose sex partners are reported to have NGU, 30%-40% harbor cervical chlamydial infection. Of men who are the sex partners of women with confirmed chlamydial MPC or PID, 25%-50% have Chlamydia isolated from the urethra. Many of these contacts are asymptomatic.

# Coexistence of Chlamydial Infection with Other STD
Approximately 1 5%-30% of heterosexual men with gonococcal urethritis have simultane ous urethral infection caused by C. trachomatis [1,15,16). An even higher proportion (25/o-50%) of women with Neisseria gonorrhoeae infection also have C. trachomatis infec tion of the cervix ( 1,15-1 7). Women who have other STD such as trichomoniasis and bacte rial vaginosis are also at increased risk of having chlamydial infection.

# Method of Contraception
Persons who use barrier methods of contraception (condom, diaphragm, diaphragm and foam) are at reduced risk for chlamydial infection relative to those who do not use any form of contraception (12). In contrast, women who use oral contraceptives have been reported to have a higher prevalence of cervical infection with C. trachomatis than women who do not use oral contraceptives ( 18). Use of intrauterine devices has not yet been investigated for its effect on rates of C. trachomatis infection.

# Pregnancy
In the United States, the prevalence of reported cervical chlamydial infection among preg nant women has varied from 2% to 37%, with most studies reporting infection rates of ap proximately 8%-12% (7 ,13,19). In general, infection has been most prevalent in the youngest age group; among unmarried women; and among inner-city, lower socioeconomic-status women.

# Health-Care Facility
Various types of health-care facilities will report different expected infection rates among women attendees. Not surprisingly, STD clinics report the highest rates of C. trachomatis in fection (an average of 20%-30% of all patients tested) (1,15). The next highest isolation rates are reported from clinics for adolescent patients (8%-26%) ( 13 ,2 0-23) and from family plan ning clinics (6%-23%) (10). Insufficient data are available to estimate expected rates in private practices, community health centers, and hospital emergency rooms.

# Lab o rato ry M etho d s
The absence of an inexpensive, simple, and reliable diagnostic test for chlamydial infection has limited control efforts. Historically, time-consuming and expensive tissue-culture tech niques have been required to definitively diagnose most C. trachomatis infections. Cytology was also available, but is only of comparable sensitivity to tissue culture in diagnosing new born conjunctivitis. In recent years antigen detection methods have offered a cost-effective al ternative to culture. Serologic methods are available, but remain principally a research tool.
Despite these encouraging improvements in diagnostic capability, current tests are not ideal. They are relatively difficult to perform, require considerable experience, and have limited application. Active investigation of new diagnostic methods for C. trachomatis continues, and antigen and antibody detection systems are improving rapidly. In such a dynamic environ ment, recommendations for the specific diagnostic methods discussed below must be flexible and should be revised as better methods become available.

# Culture
Tissue culture is presently the "gold standard" for laboratory diagnosis. Although pub lished methods are fairly standard (4), in practice many laboratories introduce variations that alter the sensitivity and specificity of the test. Rigorous adherence to standard methodology is strongly encouraged.
Two major components are needed to culture for C. trachomatis: (1) a cell-culture system * " t i -II lin o r \ f r h n i r o ic and (2) a method to identify inclusions growing in cell culture. The cell line of choice is
u ih j \*_/ a i i i c t i i u u tu 1U 0 111117 ,, ------ v , _ _ 1 1  ,, _,,
McCoy. Alternatively, a particular strain of HeLa cells (HeLa 229)
) can e us ally restricted to research laboratories. Specimen material is centnfuged o ,^2 5 H n cu ttio n 1 hour and then incubated for 2-3 days in medium containing cyclohjm de can take place in individual vials with cover slips at their ase- r ^ dictated by the plastic microtiter plates (26). The choice between t ese slightly more sensitive number of specimens a laboratory has to process; the vial ^e,hod2 S'^n 7 exDenslve and less susceptible to cross-contamination, but is more time consu usually used FA For identification, either iodine stain or fluorescent antibody (FA) sta.n " ' " ^, 2 stain offers the advantages of higher sensitivity and shorter processing i res'one requires a fluorescence microscope. The standard method for 10 ine s ainin blind passage, which increases the processing time to 4-6 days. In microtiter p a es' s  ing without passage appears equivalent to iodine staining with one blind passage e most sensitive culture method currently available involves using cycloheximide treated McCoy cells in vials in the presence of fluorescent monoclonal antibodies.
Compared with other diagnostic tests for C. trachomatis, the major advantage of tissue culture is its specificity. With this method, the organism can also be positively identified or saved for other marker studies such as immunotyping. Thus, culture is clearly the method of choice for research studies. Determining the sensitivity and specificity of the culture has not been possible since it is the reference standard for other methods; however, it is estimated that culture has a sensitivity of 80%-90%, and a specificity of 100% (28).
Culture also has several disadvantages: (1) the cost and complexity of laboratory require ments can be prohibitive; (2) specimens can be kept at 4 C for only up to 24 hours (preferably 12) before processing, or frozen at -70 C if they cannot be inoculated within 24 hours;
(3) specimens must be placed in specially prepared transport media; and (4) the cell monolay er may be contaminated with other bacteria or viruses, particularly in vaginal or rectal specimens.

# 58S

# MMWR
A u g u s t 23, 1985

# Cytologic Methods
Cytologic identification of chlamydial infections-the only method available in the period 1909-1957-is an examination of epithelial cell scrapings (e.g., conjunctival, cervical, ureth ral) on a stained smear. A modified Giemsa stain is most often used, although W right's and other standard tissue stains can be used. Infection is identified by visualizing characteristic intracytoplasmic inclusions. Alternatively, cell scrapings can be examined using FA stains (4).
The advantage of cytologic examination is clearly the simplicity of the process, particularly if light microscopy is used. The disadvantage is the poor sensitivity fo r diagnosing chlamydial infections other than neonatal conjunctivitis, for which the sensitivity of cytology compared with culture is 95%. The sensitivity of cytologic methods in identifying chlamydial adult con junctivitis is 45% for Giemsa and 85% for FA. In tests for cervical infection, the tw o stains have sensitivities of only 40% and 65%, respectively, and for urethral infection, 15% and 60% (28). Moreover, these upper levels of sensitivity can only be obtained with good specimens (many epithelial cells) and an experienced observer.
Thus, standard cytology is of little practical value as a diagnostic aid fo r genital chlamydial infection. However, tw o recent studies (29,30) suggest that the inflammatory pattern on Papanicolaou-stained cervical smears may be useful when it is used as a screening test to select patients for confirmation of infection by culture or monoclonal antibody tests, but the Papanicolaou method used alone is not satisfactory for diagnosing chlamydial infection.

# Antigen Detection
To date, two methods of antigen detection are available: (1) FA examination of a direct smear and (2) enzyme immunoassay (EIA). One example of each method is presently available commercially,- and both have undergone considerable evaluation.
However, continued revision of these tests takes place even after they become available commercially. Consequently, initial published data on efficacy may be outdated, so the most recent references should be used. Other antigen detection tests are expected to be available soon.
D irect-Sm ear FA Test (31) With this procedure, specimen material is obtained by swab and applied directly to a slide, which is fixed and then incubated with fluorescein-conjugated monoclonal antibody before being examined under a fluorescence microscope. Total processing time is usually 3 0 -4 0 min utes. Critical steps include (1) obtaining a satisfactory specimen and preparing a satisfactory smear (this can be checked before or after staining), (2) drying the specimen properly before fixing it, (3) using a high-quality fluorescence microscope, and (4) obtaining and maintaining an experienced microscopist who can recognize elementary bodies and artifacts.
Compared with culture, the sensitivity of the direct smear test is ^ 90% in most published studies, and the specificity is ^ 98%. The positive predictive value of this test has ranged from approximately 80% in populations with a Chlamydia prevalence of 10% to 95% in popu lations with a prevalence of 30% (32). Lower sensitivities and specificities are often encoun tered in situations in which specimens are less than optimal or individuals reading the slides are relatively inexperienced. In these instances, assessment of the proficiency of laboratory techniques is essential. This can be accomplished by comparing results with those obtained with tissue culture or by exchanging slides with a central reference laboratory that does proficiency testing. K
The major advantages of the direct smear test are (1) the uncomplicated transport and storage of specimens, (2) rapid processing time compared with that required for other meth ods (33), (3) a high specificity, and (4) the ability to check on adequacy of specimen collec tion (i.e., cells on the slide). Disadvantages of the method are (1) the requirement for precise specimen collection, (2) the need for high-quality fluorescence microscope equipment, (3) the need for an experienced microscopist, and (4) the relatively labor-intensive nature of the process.

# Enzym e Im m un o a ssa y (34)
This test measures antigen-antibody reactions through an enzyme-linked immunoabsorbent assay (ELISA) and requires a spectrophotometer. Processing time for specimens is ap proximately 4 hours.
Questions continue to be raised about the reliability of available ElAs for C. trachomatis. The sensitivity of the test has varied from 67% to 90%, the specificity from 92% to 97%, and the positive predictive value from 32% to 87%, depending on the population studied (35). Much of the observed disparity has been attributed to variable sensitivity of the tissue culture systems against which the EIA has been compared.
The advantages of the EIA are (1) the uncomplicated transport and storage of specimens, (2) the objective method of measurement in the laboratory, which involves standard equip ment and does not depend upon a specially trained observer, and (3) the ability to test large numbers of specimens at a time.
The disadvantages are that (1) the adequacy of the specimen cannot be checked and ( 2) th e test cannot be performed while the patient is waiting (although this is also true for the dir smear test if no fluorescence microscope is available).
It is not known whether either method of antigen detection can be use or specime sites other than the eyes and genitals (e.g., pharynx).

# Serology
Currently, Chlamydia serology has little value in routine clinical management and basically remains a research tool. Although some serologic tests are commercially available, they have not been shown to be useful in routine diagnosis.
There are tw o standard methods-complement fixation and microimmunofluorescence (MIF) (35). ELISA tests have been developed, but none are recommended for wide use (36,37). The only valid clinical uses of serologic tests are in infant pneumonia, where specific immunoglobulin M (IgM) MIF serology, when available, is the diagnostic test of choice; and in occasional cases of suspected lymphogranuloma venereum (LGV). The difficulties in prepar ing the antigen and conducting the test restrict the use of the test to a limited number of re search laboratories.

# Diagnostic Considerations
The value of rapid diagnostic tests for detecting C. trachomatis infection depends primari-V on the prevalence of disease in the population tested and the availability of other tests For ow-r.sk groups, the predictive value of a positive test is lower than for high-prevalence popu lations, even if the test is highly sensitive and specific. For example, in a population with a 5% 60S MMWR A u g u st 23,1985 prevalence, a rapid test with a 95% specificity and sensitivity will have a predictive value posi tive of 50% (meaning that there is only a 50% chance that an individual who is diagnosed as having disease actually has it). In situations in which an increase in the predictive value of a positive test is desired, in order to lower risks of incorrectly labeling persons as having STD, positive screening tests can be confirmed by culture, or culture methods can be used for screening (with an accompanying rise in cost). As new tests become available, physicians, hospital and commercial laboratorians, and public health program directors must be aware of the sensitivity, specificity, and predictive value of such tests when determining whether to use them in specific situations.
As more laboratories begin to do diagnostic testing for Chlamydia, laboratory quality con trol assumes increasing importance. Each laboratory should verify the accuracy of test meth ods other than culture by periodically comparing results with those obtained using cultures. Such comparisons are particularly important when the laboratory implements a new test method. Laboratories that do cell-culture isolation of Chlamydia should run appropriate posi tive and negative controls to verify sensitivity of the cell cultures being used and should peri odically evaluate the effectiveness of transport systems. Regional reference laboratories should be established for verification of culture results or evaluation of unexpected or discrep ant results. Proficiency testing programs should be developed for culture and other test meth ods so that laboratories can evaluate their methods using unknown specimens.

# Patient Management H igh-Risk Groups
High-risk groups should be defined using demographic profiles and the estimated or estab lished prevalence of chlamydial infection in a particular community or patient population. Al though the criteria described under Risk Assessment can be used as a guide to establishing a high-risk profile, local determinants of risk are more precise and should be identified if possi ble. Local data also provide more accurate baseline prevalences, against which the success of prevention and control strategies can be measured.
When culture results are available, they should be used in decisions concerning appropriate therapy. However, undiagnosed patients who fit an established high-risk profile should also be offered treatment, unless local or individual circumstances dictate otherwise. Patients in the following groups should immediately receive a regimen that includes effective treatment against C. trachomatis infection.

# Symptomatic Syndromes Associated with Chlamydia

# Asymptomatic Contacts of Syndromes Associated with Chlamydia
Individuals exposed through sexual contact with patients who have any of the above symptomatic syndromes (within 30 days of the onset of their symptoms or clinical evaluation) should be evaluated for STD and treated for presumptive chlamydial infection.

# Gonococcal Infection
Women with confirmed N. gonorrhoeae infection of the endocervix, heterosexual men with diagnosed gonococcal infection of the urethra, and sex partners of members of both of these groups of patients should be treated with an antimicrobial regimen that is effective against both N. gonorrhoeae and C. trachomatis infection.

# Screening
Selective screening to detect asymptomatic infection is an essential component of a suc cessful control program. Whenever possible, criteria for routine screening should be based on local determinants of risk. An appropriate diagnostic method must be selected. Diagnostic considerations for current tests/methods are discussed above. The following guidelines are provided to assist in determining which test to use.

# Screening Criteria
_ . A .. .
No single individual characteristic or practice (see p. 55S), is in itself a su icien cri erion to define which persons should be screened. However, a composite of in i v i ua a c rs _ conjunction with a community factor such as type of health-care aci ity see ' help to maximize yield from screening. Consequently, available evidence ea s o mendation that the priorities for routine screening shown below be used.

# STD Clinic
1. Individuals attending STD clinics who otherwise would not be offered antichlamydial treatment should be screened first. (The screening of asymptomatic, high-risk women should be accorded the highest priority. In general, the screening of heterosexual men should have a higher priority than screening homosexual men.) 2. Individuals with symptomatic syndromes associated with Chlamydia should be screened next. (Screening of women should be accorded higher priority than screening of men.)

# Oth er High -Risk Health -Care Faci/it y
Health-care facilities other than STD clinics may also have a high prevalence of chlamydial infections. In particular, many adolescent and family planning clinics are categorized as highrisk centers, but a wide disparity in rates of chlamydial infection may be observed in different populations." Facilities that serve high-risk populations should follow the order of screening priority for STD clinics above; those serving undetermined or low-risk populations should follow the priority below for Undetermined/Low-Risk Health-Care Facility.
Undetermined/Low-Risk Health-Care Facility 1. Persons in urban settings who are younger, have lower socioeconomic status, and have multiple sex partners, and who otherwise would not be offered antichlamydial treatment, should be screened first. (In this category of high-risk patients, women should be accorded highest priority for screening.) 2. Individuals with symptomatic syndromes associated with Chlamydia should also be screened. (Screening of women should be accorded higher priority than screening of men.)

# Diagnostic Method
Culture and two different antigen detection tests are currently the only diagnostic methods acceptable for screening for Chlamydia infection. Culture remains the most accurate method, but is costly and takes at least 2-3 days before results are available. Antigen detection tests have emerged as reasonable alternatives, but questions remain about their reliability for lowprevalence populations. Following are guidelines fo r the use of diagnostic tests in screening.
1 Culture, based upon availability, is the preferred method for routine screening. 2. Direct smear using fluorescent antibody (DFA) is the most thoroughly evaluated alterna tive to culture. However, optimal results with the currently marketed test have been achieved for high-risk women and symptomatic men by very experienced research laboratories. For other populations, test results obtained by less experienced technolo gists may not be as reliable. Consequently, DFA results should be compared periodically with those obtained through culturing. 3. Enzyme immunoassays have not been as completely evaluated as the DFA tests. The currently marketed test probably is less sensitive and specific than DFA, but the quality of results is also less likely to depend on the level of experience of laboratory personnel.
It is important that regional reference laboratories be available to monitor the perfor mance of these and other new antigen detection tests and to advise about appropriate applications and quality control problems.

# Recommendation
Screening is suggested at th e firs t p renatal visit fo r th e fo llo w in g g ro u p s o f pregnant w o m e n :
1. Adolescents (< 20 years of age)
MMWR 63S
2. Unmarried women 3. Married women who may be at high risk because of multiple sex partners or a history of other STD Screening of pregnant women who fall into any of these high-risk categories in inner-city hospitals is particularly important because of the high prevalence of asymptomatic infections among the patients served by these facilities.

# Neonates

# Ophthalmia Prophylaxis
None of the presently recommended approaches for prophylaxis against gonococcal and chlamydial ophthalmia neonatorum is completely effective. Silver nitrate is effective in prevent ing gonococcal infections but does not prevent chlamydial disease and frequently causes chemical conjunctivitis. Erythromycin is effective in preventing both gonococcal and chlamy dial ophthalmia and does not cause chemical conjunctivitis, but the topical use of this drug does not prevent nasopharyngeal chlamydial infection or pneumonia. Furthermore, eryth romycin prophylaxis is considerably more expensive than silver nitrate prophylaxis. Tetracy cline ointment has not been as extensively evaluated as has erythromycin but appears to be as effective. Whichever type of prophylaxis is used should be implemented no later than 1 hour after birth -preferably immediately after delivery since delayed application may reduce efficacy.

# Recommendation
Erythromycin (0.5%) ophthalmic ointment, tetracycline (1%) ointment, or silver nitrate should be instilled into the eyes of all neonates as soon as possible after delivery and never later than 1 hour after birth. Single-use tubes or ampules are preferable to multiple-use tubes.

# Neonatal Infection
Eighteen to fifty percent of infants born to infected mothers will have conjunctivitis be tween 1 and 3 weeks after birth (7). The symptoms are often mild, and the disease may be missed unless looked for carefully. Though considerable morbidity results acutely from the severe form of this disease, it is self-limited and does not appear to result in loss of vision. Three to eighteen percent of infants born to infected mothers will develop chlamydial pneumonia/bronchiolitis, usually at 1 -4 months of age (7). In most cases this is a mild disease, but it can be severe and require hospitalization.

# Recommendation
Screening for neonatal infection is not indicated. Newborns with conjunctivitis and afebrile pneumonia/bronchiolitis should have specimens culture-tested for C. trachomatis and be appropriately treated as recommended below. If cultures are positive, mothers (and their sex partners) of the infected children should also be treated.

# 64S

# MMWR
A u g u st 23,1985 Treatment Regimens

# CONFIRMED INFECTIONS

# Uncomplicated Urethral, Endocervical, or Rectal Infection in Adults

# Drug Regimens of Choice
Tetracycline hydrochloride (HCI): 500 mg, by mouth, 4 times a day fo r 7 days.

# OR
Doxycycline hyclate: 100 mg, by mouth, 2 times a day for 7 days.

# Alternative Regimens
(for patients for whom tetracyclines are contraindicated or not tolerated) Erythromycin base or stearate: 500 mg, by mouth, 4 times a day fo r 7 days, or eryth romycin ethyl succinate: 800 mg, by mouth, 4 times a day for 7 days.
Sulfonamides are also active against C. trachomatis. Although optimal dosages of sulfona mides for chlamydial infection have not been defined, sulfamethoxazole, 1 g by mouth, twice a day for 10 days, is probably effective.

# Follow-Up
When taken as directed, the tetracycline and erythromycin regimens listed above are highly effective (> 95% cure rates). No tetracycline-resistant Chlamydia has been described. Post-treatment cultures are not advisable if laboratory resources are limited. A positive p o s t treatment culture is more likely to represent noncompliance with treatment, failure to trea t sex partners, or laboratory error than resistance to the antibiotic. Patients who do have posi tive post-treatment cultures should be treated again according to one of the above regim ens.

# Management of Sex Partners
All persons sexually exposed to C. trachomatis infection (within 30 days after their sex partner develops symptoms or has a positive clinical evaluation) should be examined for STD and promptly treated for C. trachomatis with one of the above regimens. This group includes sex partners of individuals with sexually acquired chlamydial infection, mothers of infected newborns, and the sex partners of these mothers.

# Urogenital Infections during Pregnancy

# Drug Regimen of Choice
Erythromycin base: 500 mg, by mouth, 4 times a day for 7 days, or erythromycin ethyl succinate: 800 mg, by mouth, 4 times a day for 7 days.
Erythromycin stearate in appropriate doses may also be effective, but has not been ade quately studied.

# MMWR

# 65S

# Alternative Regimen
(for female patients who cannot tolerate the above regimen, a decreased daily dose is recommended) Erythromycin base: 250 mg, by mouth, 4 times a day for 14 days.
The optimal dose and duration of antibiotic therapy for pregnant women have not been es tablished. Currently, there are no completely acceptable alternative regimens for female pa tients who are allergic to erythromycin or otherwise cannot tolerate erythromycin. In the case of proven treatment failure, the patient should be re-treated with erythromycin according to either of the dosage schedules outlined above.

# Established Conjunctivitis of the Newborn*

# Drug Regimen of Choice
Oral erythromycin syrup: 50 mg/kg body weight/day in 4 divided doses for 14 days.
There is no indication that topical therapy provides additional benefit. If inclusion conjunc tivitis recurs after therapy, erythromycin treatment should be reinstituted for an additional 1 -2 weeks.

# Pneumonia among Infants

# Drug Regimen of Choice
Oral erythromycin syrup: 50 mg/kg/day in 4 divided doses for 14 days.

# CHLAM

# YDIA-ASSOCIATED SYNDROM ES

# Nongonococcal Urethritis
NGU can be diagnosed for a male patient if tests for N. gonorrhoeae are negative and the patient has objective evidence of urethritis. Objective evidence of urethritis includes a visibly abnormal discharge, pyuria defined as > 10 polymorphonuclear leukocytes (PMN) per high dry field in the sediment of a first-voided urine specimen, or > 4 PMN per oil immersion field in a Gram-stained urethral smear. Approximately 50% of the cases of urethritis not associated with N. gonorrhoeae are caused by C. trachomatis. NGU requires prompt antimicrobial treat ment of the patient and evaluation and treatment of any sex partners.

# Drug Regimens of Choice
Tetracycline HCI: 500 mg, by mouth, 4 times a day for 7 days. Alternative Regimen (for patients for whom tetracyclines are contraindicated or not tolerated) Erythromycin base or stearate: 500 mg, by mouth, 4 times a day fo r 7 days, or eryth romycin ethyl succinate: 800 mg, by mouth, 4 times a day for 7 days.
Sulfonamides are not suitable for treatment fo r clinical syndromes when Chlamydia cul tures are not performed, since they may not be effective against Ureap/asma urea/yticum and other organisms that cause nonchlamydial genital infection.

# Management of Sex Partners
All persons who are sex partners of patients with NGU (within last 30 days) should be examined for STD and treated promptly with one of the above regimens.

# Follow-Up
Patients should be advised to return for follow-up medical care if symptoms persist or recur.

# Mucopurulent Cervicitis*
The presence of mucopurulent endocervical exudate often reflects cervicitis due to chlamydial and/or gonococcal infection. If N. gonorrhoeae is found on Gram stain or culture of endocervical or urethral discharge, a treatment regimen effective against both gonococcal and chlamydial infection should be used. When only chlamydial infection is proven or suspect ed, therapy should consist of one of the regimens below.

# Drug Regimens of Choice
Tetracycline HCI: 500 mg, by mouth, 4 times a day for 7 days.
OR Doxycycline: 100 mg, by mouth, twice a day for 7 days.

# Alternative Regimens
(for patients for whom tetracyclines are contraindicated or not tolerated) Erythromycin base or stearate: 500 mg, by mouth, 4 times a day fo r 7 days, or eryth romycin ethyl succinate: 800 mg, by mouth, 4 times a day for 7 days.

# Management of Sex Partners
Men exposed to women with MPC attributed to chlamydial infection should be evaluated for STD and treated with one of the above regimens. If N. gonorrhoeae is found, treatment should be with a regimen effective against uncomplicated gonococcal and chlamydial infection.
-Criteria for presumptive diagnosis include (1) m u c o p u ru le n t s e c re tio n from the endocervix, which is usually yellow or green when viewed on a white cotton-tipped swab (positive swab test); (2) ^ 10 p o ly m orp h o n ucle a r le u k o c y te s per microscopic oil immersion field (X 1,000) in a Gram-stained smear of en docervical secretions; and (3) c e rv ic itis , determined by cervical friability (bleeding when the first swab culture is taken) and/or by erythema or edema within a zone of cervical ectopy. Acute PID refers to the acute clinical syndrome attributed to the ascending spread of mi croorganisms, unrelated to pregnancy or surgery, from the vagina and endocervix to the endo metrium, fallopian tubes, and/or contiguous structures. Clinical findings for most patients with PID include lower abdominal tenderness, adnexal tenderness, and pain induced by lateral motion of the uterine cervix. Many cases of PID are caused by more than one organism. Causative agents include C. trachomatis, N. g o n anaerobic bac oides and gram-positive cocci), and facultative gram-negative rods (such as Actinom yces israelii, and Mycoplasma horn inis.
These agents cannot usually be differentiated in individual patients. Consequently, treat ment regimens should be used that are active against the broadest range of the pathogens. CDC has already published comprehensive guidelines regarding criteria for hospitalization, rationale for selection of antimicrobials, and general treatment regimens for the major patho gens associated with PID (39): Below are examples of specific combinations of regimens for optimal coverage for C. trachomatis and for adequate coverage for the other common causa tive agents.

# Inpatient Treatment
Doxycycline: 100 g, intravenous (IV), 2 times a day.

# PLUS
Cefoxitin: 2.0 g, IV, 4 times a day. Continue drugs IV for at least 4 days and at least 48 hoursa*r^a p T - Cnt'nUe doxycycline 100 mg, by mouth, 2 times a day, to complete 10-V

# Ambulatory Treatment
Cefoxitin: 2.0 g, intramuscular (IM), OR amoxicillin: 3.0 g, by mouth, OR ar"P 3.5 g, by mouth, OR aqueous procaine penicillin G: 4.8 million units, IM, at 2 sites (eac along with probenecid: 1.0 g, by mouth), OR ceftriaxone: 250 mg, IM FOLLOWED BY Doxycycline: 100 mg, by mouth, 2 times a day for 10-14 days.
Tetracycline HCI 500 mg, by mouth, 4 times a day, can also be used, but is less active against certain anaerobes and requires more frequent doses; both factors represent draw backs in treatment of PID.

# Management o f Sex Partners
All persons who are sex partners of patients with PID (within the 30 days prior to onset of their symptoms or positive clinical evaluation) should be examined for STD and treated promptly with a regimen effective against uncomplicated gonococcal and chlamydial infection.
A CDC update of these Guidelines is in press.

# 68S

# MMWR
A u g u st 23, 1985

# Follow-Up
All patients treated as outpatients should be clinically reevaluated in 4 8 -7 2 hours. Those not responding favorably should be hospitalized. Patients should also be reevaluated after they complete treatment.

# Intrauterine Device
The intrauterine device (IUD) is a risk factor for the development of PID. Although the exact effect removing an IUD has on the response of acute salpingitis to antimicrobial therapy and on the risk of recurrent salpingitis is unknown, it is recommended that the IUD be removed as soon as possible after antimicrobial therapy has been initiated. When an IUD is removed, contraceptive counseling is necessary.

# Acute Epididymo-Orchitis
Acute epididymo-orchitis has two forms: (1) a sexually transmitted form usually associat ed with urethritis and commonly caused by C. trachomatis and/or N. gonorrhoeae and (2) a nonsexually transmitted form associated with urinary tract infections caused by Enterobacteriaceae or other nonsexually transmitted uropathogens. Urine should be examined by Gram stain and culture to exclude bacteruria in all patients, including those with urethritis. An impor tant part of the differential diagnoses is testicular torsion, a surgical emergency.
Sexually transmitted epididymo-orchitis usually affects young adults and is associated with presence of clinical or subclinical urethritis, absence of underlying genitourinary patholo gy, and absence of gram-negative rods on Gram stain of urine.

# Drug Regimens of Choice
Amoxicillin: 3.0 g, by mouth, OR ampicillin: 3.5 g, by mouth, OR aqueous procaine peni cillin G: 4.8 million units, IM at 2 sites (each along with probenicid. 1.0 g, by mouth), OR spectinomycin: 2.0 g, IM, OR ceftriaxone: 250 mg, IM

# FOLLOWED B Y
Tetracycline HCI: 500 mg, by mouth, 4 times a day for 10 days.

# OR
Doxycycline: 100 mg, by mouth, 2 times a day for 10 days.

# Alternative Regimens
(for patients for whom tetracyclines are contraindicated or not tolerated) Erythromycin base or stearate: 500 mg, by mouth, 4 times a day fo r 7 days, or eryth romycin ethyl succinate . 800 mg, by mouth, 4 times a day for 7 days.

# Management of Sex Partners
Sex partners of patients with sexually transmitted acute epididymo-orchitis (diagnosed within 30 days of exposure) should be examined for STD and promptly treated with a regimen effective against uncomplicated gonococcal and chlamydial infection.

# MMWR

# 69S

# Fo llow -U p
Failure to improve within 3 days requires reevaluation of diagnosis/therapy and considera tion fo r hospitalization.

# Patient Education

# Patient Counseling
The effective management of chlamydial infection includes counseling of patients. Such counseling should be designed to influence specific behavior that will contribute to successful therapy, disease intervention, and prevention. Patient handouts designed for easy comprehen sion are an efficient way of conveying basic information. These messages should be rein forced by practitioners through discussions with patients that are tailored to the individual and provide an opportunity for questions.

# Recommendation
Practitioners should provide counseling to patients regarding their disease, its treatment, and the overall responsibility of the patient in the process. Information conveyed to patients should at least include:
1 Instructions for taking medication, including the dosage, timing, and length of the regimen. Patients must clearly understand that they must continue to take medication according to schedule, despite abatement of symp toms. 2. Advice regarding follow-up for side effects or other difficulty with medica tion, continued or worsened symptoms, and test of cure, if indicated. Suggestion to abstain from sexual activity until medication is completed by both patient and partner. If this is not possible, patients should be en couraged to use condoms until treatment is completed. Suggestion to cease sexual activity immediately if the same or other STD symptoms recur, and to return to the practitioner/clinic with the steady sex partner. 5. Suggestion to regularly use barrier methods, particularly condoms, to pre vent chlamydial infection and other STD.

# Sex Partner Referral
The sex partners of patients with chlamydial infection should be referred for medical care through the efforts of individual patients, or through a disease intervention specialist (DIS) Al though the latter process is time-consuming, it may be very effective. However, locating and referring sex partners through a DIS is clearly not feasible for all patients with chlamydial in fection and the C/?/aA7?yc//3-associated syndromes discussed above. First priority for interviewing/counseling efforts by a DIS should be given to patients with proven chlamydial infection. The contract method of sex partner referral should be used, with the patient assuming referral responsibility whenever possible. The referral of sex partners by the patient is a more practical approach in terms of human resources, but the effectiveness of this practice has not been evaluated among Chlamydia patients. Nevertheless, attempts must be made to capitalize on patients' knowledge of and persuasiveness with their own sex partners.

# Recommendation
Patients with chlamydial infection should be encouraged to refer all persons with whom they had sexual encounters in the 30 days prior to onset of their symptoms or clinical evaluation. (Approximately 94% of sex partners to NGU pa tients brought to treatment have been exposed within 30 days.)

# Prevention
Of all possible Chlamydia control approaches, successfully preventing the initial infection remains the most effective. Education of the public and of health professionals is essential for prevention at all three levels (primary, secondary, tertiary), especially in the absence of an ef fective vaccine.

# Professional Training/Education
Providers of health care can play a leading role in reducing the incidence of C. trachomatis infection and its complications. Timely diagnosis and appropriate treatment of chlamydial in fection by practitioners will prevent further transmission and minimize the risk that the infect ed individual will have adverse consequences. Additionally, clinicians are in a position to in fluence a patient to avoid behavior likely to result in transmitting disease or in being reinfected. STD education for health-care professionals should promote the following:
1 Recognizing Ch/amydia-assoc\aXe6 syndromes and high-risk patients. 2. Following recommended STD treatment guidelines. 3. Reporting cases promptly and completely. 4. Counseling patients to refer all sex partners for medical evaluation, to take all medica tion as prescribed, and to modify their behavior so as to reduce the risk of future infection.

# Recommendation
1. Professional recognition should be enhanced by incorporating knowledge about chlamydial infection into education and training programs fo r physi cians, nurses, laboratory personnel, and allied health professionals (such as physician assistants). 2. Organizations for health professionals, academic centers, colleges, and societies should be encouraged to formally support the chlamydial preven tion and control efforts by (a) providing appropriate continuing medical/ professional education courses about chlamydial infections at national/regional/local meetings and (b) encouraging health-professional journalsespecially official organizational p u b lications-to publish chlamydial policy guidelines and clinical reviews and research papers on Chlamydia and as sociated infections.

# MMWR

# 71S
Public Education/Health Promotion Education of the public is necessary to provide a high level of awareness of chlamydial in fections (and other STD) and to influence people to know and communicate about the preven tion, recognition, and treatment for Chlamydia; to support control efforts; and to reduce their personal risk of acquiring or transmitting a chlamydial infection. Accumulating evidence sug gests that public education can influence individuals to reduce their risk of acquiring an STD by changing sexual practices.
One such practice that should be encouraged is the use of barrier methods of contracep tion. Barrier methods of contraception (condoms and diaphragms) are known to provide pro tection against Chlamydia infection and other STD when used properly. The effectiveness of spermicides in preventing Chlamydia infection has not been determined. However, spermi cides do not enhance infection and do achieve some measure of protection when used in con junction with a diaphragm or condom.

# Recommendation
Disseminate the following information to the public: 1. Risks of chlamydial infection associated with sexual activity, especially when multiple partners are involved. 2. Role of barrier methods of contraception for personal prophylaxis to pre vent chlamydial infection and other STD.

# Surveillance
A fundamental requisite for control and prevention of chlamydial infection is a national sur veillance system, since it provides quantitative estimates of incidence and prevalence, a basis for determining secular trends, and a tool for evaluating control efforts. Current methods for diagnosis now permit the establishment of a multitiered, multifocal disease surveillance system. The tiers are local, state, and national. The foci include subgroups at special risk, clini cal syndromes of particular importance, and the general population.
A national surveillance system will require state reporting laws and/or regulations to pro vide the necessary support for prevention activities. Reporting laws promote and legitimize the involvement of public health authorities in assuring adequate individual patient management-including referral of sex partners-and may facilitate other activities such as screening and education. Moreover, case reporting provides a uniform basis for describing the extent and trpnH nf Hicoaco

# 72S

# MMWR
A u g u st 23,1985 Prevention and control activities for chlamydial infections have been proposed in this document, although the inadequacies in current diagnostic methods are acknowledged. In particular, patient management, including sex partner referral, is recommended for selected C h la m y d ia -associated clinical diagnoses (not dependent on the results of a laboratory test for C h la m y d ia ). Similarly, case reporting should include selected clinically diagnosed conditions associated with C h la m y d ia infection in addition to laboratory-diagnosed C h la m y d ia infection. Pending development of nationwide laboratory capability for identifying C h la m y d ia , condi tions should be selected that will best serve as indices fo r chlamydial infection, and that repre sent important public health problems in their own right. Reporting of clinically diagnosed conditions should augment rather than replace reporting of laboratory-diagnosed problems, since continuing efforts to develop a national laboratory capability will greatly enhance oppor tunities for ongoing improvements in patient management and public health interventions.
Although a national surveillance system should be based on case reporting, additional ap proaches, involving classical statistical methods, should be utilized, at least at the national level, to provide extent and trend estimates less vulnerable to the biases inherent in estimates based on case reports.

# Recommendation

#No absolute criteria exist for defining the clinical syndromes of NGU and PID/AS, but a constellation of signs and symptoms may be suggestive. For NGU, these include a patient with dysuria, white cells on Gram stain of urethral smears, and/or frank urethral discharge, in the presence of negative tests for gonorrhea. PID/AS is more protean in its manifestations, and the diagnosis ultimately rests on the judg ment of the attending clinician. Usual features include a combination of (1) lower abdominal pain, (2) adnexal tenderness, (3) adnexal mass, (4) pain on cervical motion, (5) mucopurulent discharge, and (6) temperature elevation. No single combination is pathognomonic.