Pediatric Annals

Neisseria gonorrhoeae in Children

David L Ingram, MD

Abstract

Gonococcal infections in neonates and children are important to recognize, evaluate, and treat for a variety of reasons. They not only may cause permanent sequelae, but also may be indicators of maternal and paternal infection, or of sexual abuse. Furthermore, neonates or children with gonococcal infections may be at high risk for other serious infections caused by Chlamydia trocho' matis, human immunodeficiency virus (HIV), hepatitis B virus, or syphilis. In the United States, there are an estimated 1 million new cases of gonorrhea a year, mostly found in adults, and in many institutions, more children are being identified with gonococcal infections. With increased promiscuity and selling sex for drugs in the adult population, and decreased public health resources to track down and treat contacts of gonorrhea cases, more adults are becoming infected and, in turn, are infecting children. This article describes the clinical syndromes, the epidemiology, the evaluation, and the current treatment of infections caused by Neisseria gonorrhoeae in neonates and children.

CLINICAL SYNDROMES

Neonates

Neonatal gonococcal infections almost always come from infected maternal vaginal secretions and are acquired during the birth process.

Gonococcal Ophthalmia Neonatorum. Gonococcal ophthalmia neonatorum may range from a mild to a severe infection. It starts with a watery discharge from the eye, which, in a short time, usually becomes thick, mucopurulent, and may contain blood.1 Edema of the eyelids and conjunctiva may be severe and, if untreated, be followed by edema and ulceration of the cornea, perforation of the globe, and blindness. The infection also may become systemic.1 The incubation period is usually 2 to 5 days but may be as long as 25 days. Infection may develop despite prophylaxis of the eyes with 1% silver nitrate, 0.5% erythromycin ophthalmic ointment, or 1% tetracycline ointment.

Rapid presumptive identification of N gonorrhoeae (gram-negative intracellular diplococci in pairs) should be done from a conjunctival swab. Treatment should be started while awaiting culture results from blood culture, and conjunctival, oropharyngeal, vaginal, and rectal swabs. False-positive Gram stains may be due to conjunctivitis caused by other Neisseria species or Moraxella catarrhalis. The differential diagnosis of ophthalmia neonatorum includes chemical conjunctivitis caused by topical silver nitrate and infectious conjunctivitis caused by C trachomatis, Staphylococcus aureus, Hemophilus influenzae, Streptococcus species, enteric bacteria, and herpes simplex.

Scalp Abscesses. Neisseria gonorrhoeae may infect the scalp where the surface of the skin has been broken by a fetal monitoring electrode.1 The local infection may cause cellulitis or necrosis and may spread to a systemic infection. Wound and blood cultures may be positive. The differential diagnosis includes infections caused by Staphylococcus species, Streptococcus agalactiae, H influenzae, enteric bacteria, and Ureaplasma urealyticum.

Vaginitis, Proctiüs, and Oropharyngeal Infections. Cases of infection of the vagina, rectum, or the oropharynx of the newborn by infected maternal vaginal secretions have been reported.2 These infections are usually asymptomatic, although purulent secretions may be seen from the vagina or rectum. A diagnosis is made by culturing these areas.

Systemic Infections. In neonates, N gonorrhoeae may spread from local infections to cause pneumonia, sepsis, arthritis, or, rarely, meningitis. These may lead to severe infection, resulting in serious sequelae or death. Approximately 1% of neonates with local gonococcal infections will develop systemic infections. In rare cases, pneumonia and gastritis may be seen when there has been prolonged rupture of the membranes prior to delivery.3 Gonococcal arthritis in neonates commonly starts in the first to fourth week of life. The neonates may be irritable and febrile. Some have rashes and superficial abscesses.4 Then, joint swelling develops that more commonly involves multiple joints, including those of the hands, knees, ankles, and wrists. Arthritis may present as…

Gonococcal infections in neonates and children are important to recognize, evaluate, and treat for a variety of reasons. They not only may cause permanent sequelae, but also may be indicators of maternal and paternal infection, or of sexual abuse. Furthermore, neonates or children with gonococcal infections may be at high risk for other serious infections caused by Chlamydia trocho' matis, human immunodeficiency virus (HIV), hepatitis B virus, or syphilis. In the United States, there are an estimated 1 million new cases of gonorrhea a year, mostly found in adults, and in many institutions, more children are being identified with gonococcal infections. With increased promiscuity and selling sex for drugs in the adult population, and decreased public health resources to track down and treat contacts of gonorrhea cases, more adults are becoming infected and, in turn, are infecting children. This article describes the clinical syndromes, the epidemiology, the evaluation, and the current treatment of infections caused by Neisseria gonorrhoeae in neonates and children.

CLINICAL SYNDROMES

Neonates

Neonatal gonococcal infections almost always come from infected maternal vaginal secretions and are acquired during the birth process.

Gonococcal Ophthalmia Neonatorum. Gonococcal ophthalmia neonatorum may range from a mild to a severe infection. It starts with a watery discharge from the eye, which, in a short time, usually becomes thick, mucopurulent, and may contain blood.1 Edema of the eyelids and conjunctiva may be severe and, if untreated, be followed by edema and ulceration of the cornea, perforation of the globe, and blindness. The infection also may become systemic.1 The incubation period is usually 2 to 5 days but may be as long as 25 days. Infection may develop despite prophylaxis of the eyes with 1% silver nitrate, 0.5% erythromycin ophthalmic ointment, or 1% tetracycline ointment.

Rapid presumptive identification of N gonorrhoeae (gram-negative intracellular diplococci in pairs) should be done from a conjunctival swab. Treatment should be started while awaiting culture results from blood culture, and conjunctival, oropharyngeal, vaginal, and rectal swabs. False-positive Gram stains may be due to conjunctivitis caused by other Neisseria species or Moraxella catarrhalis. The differential diagnosis of ophthalmia neonatorum includes chemical conjunctivitis caused by topical silver nitrate and infectious conjunctivitis caused by C trachomatis, Staphylococcus aureus, Hemophilus influenzae, Streptococcus species, enteric bacteria, and herpes simplex.

Scalp Abscesses. Neisseria gonorrhoeae may infect the scalp where the surface of the skin has been broken by a fetal monitoring electrode.1 The local infection may cause cellulitis or necrosis and may spread to a systemic infection. Wound and blood cultures may be positive. The differential diagnosis includes infections caused by Staphylococcus species, Streptococcus agalactiae, H influenzae, enteric bacteria, and Ureaplasma urealyticum.

Vaginitis, Proctiüs, and Oropharyngeal Infections. Cases of infection of the vagina, rectum, or the oropharynx of the newborn by infected maternal vaginal secretions have been reported.2 These infections are usually asymptomatic, although purulent secretions may be seen from the vagina or rectum. A diagnosis is made by culturing these areas.

Systemic Infections. In neonates, N gonorrhoeae may spread from local infections to cause pneumonia, sepsis, arthritis, or, rarely, meningitis. These may lead to severe infection, resulting in serious sequelae or death. Approximately 1% of neonates with local gonococcal infections will develop systemic infections. In rare cases, pneumonia and gastritis may be seen when there has been prolonged rupture of the membranes prior to delivery.3 Gonococcal arthritis in neonates commonly starts in the first to fourth week of life. The neonates may be irritable and febrile. Some have rashes and superficial abscesses.4 Then, joint swelling develops that more commonly involves multiple joints, including those of the hands, knees, ankles, and wrists. Arthritis may present as pseudoparalysis of an extremity, but it seldom permanently damages the joints.

Noted sequelae include dislocation of the hips, contractures, changes in the shape of the femoral head and neck, and erosion of the superior borders of the acetabulum. In females, arthritis is usually accompanied by vaginitis. Gonococcal osteomyelitis also is seen.4 The diagnosis of gonococcal arthritis is made by culturing the synovial fluid and blood, and Gram staining the synovial fluid. When the diagnosis is suspected, cultures of the oropharynx, vagina/urethra, and rectum should be performed before treatment is started.

Preadolescent Children

Clinical gonococcal infections in children past the neonatal period almost always come from sexual contact.

Vaginitis. Gonococcal vaginitis is the most common gonococcal infection in children. The natural history of this type of infection was described in the preantibiotic era when it was very difficult to treat.5 The incubation period is usually only a few days. The infection may remain asymptomatic, but usually the child develops a white, yellow, or green milky or thick, sometimes malodorous, vaginal discharge that may be accompanied by labial erythema.6 The discharge may last for many months, become serous, and then disappear, but the child may still be colonized. If a colonized child gets scarlet fever, measles, or chickenpox, which cause the vaginal tissue to become inflamed, the gonococcal infection may become symptomatic again.5 The infection may last at least 8 months and possibly longer.5

In a prospective study of 1307 female children, aged 1 to 12 years, who were being evaluated for sexual abuse, we found 3% had gonococcal vaginitis.7 Five of the 37 children with gonococcal vaginitis were asymptomatic and had neither a discharge on examination nor a history of a discharge in the previous 6 months. For this reason, the absence of a discharge does not mean that cultures for N gonorrhoeae should not be done. Other studies of children evaluated for sexual abuse revealed 5% to 20% had a gonococcal infection, most frequently gonococcal vaginitis.1 Nehseria gonorrhoeae infects the entire vaginal tract and hymenal tissue in prepubertal children. Therefore, cultures need to be taken only of the hymenal tissue and the first few millimeters of the vagina. Deep vaginal or cervical cultures are not necessary. A speculum examination of the vagina should only be done if there is a concern about a foreign body, vaginal tears, or vaginal bleeding of unknown etiology.

The differential diagnosis of the causes of vaginitis in children is extensive and includes chemical irritants, poor hygiene, foreign bodies, and infections caused by viruses, bacteria, fungi, and parasites. Every case of vaginitis in a child should include a culture for N gonorrhoeae, as one cannot clinically distinguish gonococcal vaginitis from vaginitis caused by other etiologies. Before treatment, oropharyngeal and rectal cultures for N gonorrhoeae should be performed.

Urethritis. Gonococcal urethritis may be seen in boys and girls. It may be asymptomatic or present with a mucopurulent discharge. The child may have dysuria and pyuria with a sterile urine culture when routine urine culturing techniques for normal urinary tract pathogens are used. A Gram stain of the discharge followed by a urethral meatal culture will make the diagnosis. A deep urethral culture is not necessary in children. The prevalence of asymptomatic urethritis in boys is unknown, as it is fairly uncommon. In our prospective study of 231 boys evaluated for possible sexual abuse, two had urethritis, one of which was asymptomatic.7

Pelvic Inflammatory Disease. In prepubertal children, vaginal infection may spread and cause salpingitis, peritonitis, and perihepatitis in about 6% of cases. In children, it is often very difficult to distinguish pelvic inflammatory disease from appendicitis or a ruptured appendix. Often, the diagnosis is made during laparotomy for possible appendicitis. Signs and symptoms include abdominal pain in the lower abdomen, fever, rebound tenderness, decreased bowel sounds, localized pain on rectal examination, and a vaginal discharge or a history of a vaginal discharge.8

In a girl with suspected appendicitis, inspect the vaginal area for a discharge. While awaiting culture results, a vaginal discharge Gram stain should be performed. Finding gram-negative diplococci makes one suspect pelvic inflammatory disease, realizing there may be other bacteria that look like N gonoT' rhoeae in a vaginal discharge Gram stain. Acute pelvic inflammatory disease may be caused by C trachomatis or U urealyticum. Chronic fallopian tube scarring may lead to abscesses containing mixed aerobic and anaerobic bacterial flora.1

Conjunctivitis. Gonococcal conjunctivitis in children may be mild or as severe as gonococcal ophthalmia neonatorum.9 There may be swelling of the conjunctiva and eyelids with a profuse mucopurulent discharge. The source often is autoinoculation or inoculation by others whose fingers are contaminated by gonococci from a vaginal discharge. In two children seen at our institution, gonococcal conjunctivitis was the presenting sign of sexual abuse. On further examination, both girls were found to have gonococcal vaginitis. If a Gram stain of the profuse conjunctival discharge followed by a culture had not been done and the children treated only with antibiotic ophthalmic drops, the diagnosis would have been missed. A presumptive diagnosis of gonococcal conjunctivitis can be made by a Gram stain of the discharge while awaiting culture results.

Treatment for gonorrhea should be started based on the Gram stain, realizing there are going to be false-positive Gram stain results caused by other Neisseria species and M catarrhalis. Evaluation of all cases of moderate to severe conjunctivitis should include a workup for N gonorrhoeae.

Rectal and Oropharyngeal Infection. These infections are less common than vaginitis, although rectal infections ate more common than oral infections. Infections in both sites usually are asymptomatic. Rectal infections are seen in about half of children with gonococcal vaginitis and may be seen without accompanying vaginitis.10 When symptomatic, rectal infections may exhibit perianal itching or burning, some purulent staining of the underwear, and mucous or mucopurulent discharge in the stools. In more severe cases, there may be a copious, purulent anal discharge with burning or stinging rectal pain, blood or mucous in stools, and tenesmus. Ischiorectal abscesses may be present.

Oropharyngeal infections may show an exudative tonsillitis, soft-palate swelling, and erythema.11 Symptoms of pharyngeal pain may last for weeks. In our survey of 41 children with gonococcal infections, 39 had genital infections, 26 had rectal infections, and 2 had oropharyngeal infections.7 Both children with oropharyngeal infections also had genital and rectal infections, although isolated oropharyngeal infections have been reported. There is a single report of a gonococcal gum abscess in a 10-week-old infant.12 The diagnoses of rectal and oropharyngeal infections are made by culturing swabs of these areas, which is done as the routine workup of any suspected gonococcal infection or sexual abuse evaluation.

Disseminated Gonococcal Disease. Disseminated gonococcal disease in children may include sepsis, monoarticular or polyarticular arthritis, tenosynovitis, and myositis.1 In one review, gonococcal arthritis was found to be the second most common type of bacterial arthritis between 2 and 5 years of age, and the third most common type between 6 and 15 years of age.13 As in adults, migratory polyarthritis may be noted initially before infection settles into a single joint.1 Hemorrhagic or pustular lesions may be noted, especially on the hands and feet, at the same time the gonococcal arthritis is present. When gonococcal arthritis is being considered in the differential diagnosis, a Gram stain of the synovial fluid and cultures of synovial fluid, blood, the oropharynx, the rectum, and the vagina/ureuSrea should be performed before treatment is started. Cases of gonococcal meningitis, endocarditis, myocarditis, and hepatitis have been reported in adults but rarely, if ever, in children.1

EPIDEMIOLOGY

In the first month of life, gonococcal infections are acquired primarily from the mother's birth canal, although sexual abuse is still a possibility. In the first year of life, it may be difficult to determine whether the infection came from the mother or was acquired by sexual contact, as it is unclear how long a neonate may carry the organism after being colonized by the mother. After the first year of life, almost 100% of gonococcal infections are found to have resulted from sexual contact with an adult or a child with gonococcal disease.14 A child with gonorrhea must be thoroughly interviewed by a professional who is skilled in sexual abuse evaluations in order to identify possible contacts, who are usually members of the child's extended family. If no history of sexual contact is obtained, multiple interviews over time are necessary. In our series of cases of gonococcal disease in children, only 18% of the children who gave a history of sexual contact did so on the first interview.6 Two girls told us about their sexual contact 8 years later when they were no longer afraid of the sexual abuser.

Major problems incurred in identifying the sexual contact arise when multiple possible contacts in the extended family are found to be infected, when the child is very young and difficult to understand, when the prime suspect refuses to be cultured or has received treatment that is effective for gonorrhea, or when the child and the child's family are afraid to disclose information because of violent threats by the offender. In cases in which children refuse to reveal their contact, we have made a list of all their possible contacts in their extended family, had the Public Health Department culture these people, and narrowed our interviewing of the family to questions about persons who are culture positive or had been treated recently. Faced with positive culture results, family members are often more helpful. Identifying contacts may be difficult. Referral of cases to professional child abuse evaluation centers, if available, may be of great assistance.

Are there rare cases of childhood gonococcal infections that are not sexually transmitted? An interesting review of childhood gonococcal infections by Hamilton5 in 1908 describes hospital epidemics, as well as an epidemic of gonococcal vaginitis in an orphanage where up to 20 to 30 girls bathed in a giant tub at one time. Eventually, 65 girls who bathed in the tub acquired gonococcal vaginitis, presumably from someone who shared the tub. At the turn of the century, gonococcal vaginitis in children sometimes spread rapidly through hospital wards for children with scarlet fever or measles but not through other wards that had other infectious diseases. In 1907 and 1908, there were five to six epidemics of gonococcal vaginitis in the scarlet fever wards of the Cook County Hospital involving 82 infants and little girls. There was a case made for the spread of the disease being caused by the infected fingers of nurses handling one child after another.5 The problem with these reports and others postulating that one can catch gonorrhea from toilet seats and other inanimate objects is that, in these reports, the children were not questioned about sexual contact.15,16

A mid- 1920s hospital epidemic of systemic gonococcal disease involving 67 neonates in a 1 -month period with 53 developing septic arthritis described by Cooperman probably was caused by some sort of nonsexual contact, although the source was never identified.4 There are cases of isolated gonococcal conjunctivitis that may have been acquired from contaminated adult fingers or inanimate objects but this has not been proven.9 Studies of toilet seat use by children with gonococcal vaginitis have not shown spread of infection to other children.17 The topic of nonsexual transmission recently has been reviewed with the recommendation that cases in which a sexual contact cannot be identified should be diagnosed as "gonococcal infection, how acquired unknown" rather than "due to contamination."15 Always assume there is a sexual contact in cases of childhood gonorrhea and make every effort to find it.

DETECTING THE ORGANISM

Because of the clinical, social, and legal implications involved, proper identification of N gonorrhoeae is imperative. As mentioned before, doing a Gram stain of infected body fluids looking for gram-negative diplococci attached side by side is sensitive but not specific, as other Neisseria species and M coiarrhaUs look the same as N gonorrhoeae. Swabs of infected body fluids or exudates need to be cultured immediately on warm chocolate agar and modified ThayerMartin agar and incubated in an atmosphere containing carbon dioxide, or placed in carrying media with a carbon dioxide-enriched atmosphere for transport. Identification is made by colony morphology, Gram stain, and a positive oxidase test, followed by two tests that involve different principles (eg, biochemical, enzyme substrate, or serologic methods).18 Isolates should be preserved in case additional or repeat testing is needed. In children beyond the neonatal period, it probably would be best to send the gonococcal isolates to the state public health laboratories for confirmation, as misidentification could cause enormous stress on the child's family and lead to legal action against the doctor caring for the child.

Unfortunately, misidentification is common. One study found that one third of strains identified as N gonorrhoeae by clinical laboratories were not confirmed as N gonorrhoeae when evaluated by the Centers for Disease Control and Prevention (CDC).19 Rapid tests such as deoxyribonucleic acid probes or enzyme immunoassay tests should never be used when evaluating children because they sometimes produce false-positive results.18 If N gonorrhoeae is suspected from a Gram stain or is clinically isolated from any site, as many other sites as possible should be cultured for this organism before treatment is started. These sites include the oropharynx, rectum, and vagina/ urethra. A diagnosis will be impossible to make by culture once treatment is started, and a diagnosis of sexual abuse may be missed if cultures are not done properly.

TREATMENT

Treatment for gonococcal infections in neonates and children recently has been updated by the CDC.18 Their treatment recommendations are as follows.

Gonococcal Infections in Neonates

* Gonococcal ophthalmia neonatorum: ceftriaxone 25 to 50 mg/kg intravenously (IV) or intramuscularly (IM) in a single dose not to exceed 125 mg. Ceftriaxone should be administered cautiously among infants with elevated bilirubin levels, especially premature infants.

* Disseminated gonococcal infections (including sepsis, arthritis, meningitis, or any combination thereof): ceftriaxone 25 to 50 mg/kg/day in a single daily dose for 7 days, with a duration of 10 to 14 days if meningitis is documented or cefotaxime 25 mg/kg every 12 hours for 7 days, with a duration of 10 to 14 days if meningitis is documented.

* Prophylactic treatment of infants whose mothers have untreated gonococcal infections and an asymptomatic infant: ceftriaxone 25 to 50 mg/kg IV or IM, not to exceed 125 mg in a single dose.

Treatment of Gonococcal Infections in Children Weighing ≤45 kg

* Uncomplicated gonococcal vaginitis, cervicitis, urethritis, pharyngitis, proctitis, or conjunctivitis: ceftriaxone 125 mg IM in a single dose.

* Disseminated infection, bacteremia, arthritis, or meningitis: ceftriaxone 50 mg/kg (maximum dose 1 g) IM or IV in a single dose daily for 7 days. For meningitis, the duration of treatment is 10 to 14 days with a maximum dose of 2 g.

Treatment of Gonococcal Infections in Children Weighing >45 kg

* Uncomplicated gonococcal vaginitis, cervicitis, urethritis, pharyngitis, or proctitis: ceftriaxone 125 mg IM in a single dose.

* Conjunctivitis: ceftriaxone 1 g IM and lavage the eye with saline once.

* Disseminated infection, bacteremia, tenosynovitis, or arthritis: ceftriaxone 1 g IM or IV every 24 hours for 7 days.

* Disseminated infection, meningitis, or endocarditis: ceftriaxone 1 to 2 g IV every 12 hours for 10 to 14 days for meningitis and at least 4 weeks for endocarditis.

Other Considerations

Only parenteral cephalosporins are recommended for use among children. Ceftriaxone is approved for all gonococcal infections among children. Oral cephalosporins (ie, Cefixime, cefuroxime axetil, and Cefpodoxime) have not received adequate evaluation in the treatment of gonococcal infection in pediatric patients to recommend their use. The discomfort of ceftriaxone IM may be reduced by using a 1% lidocaine solution as a diluent.

All children with gonococcal infections also should be evaluated for coinfection with C trachomatis, syphilis, and in some instances hepatitis B virus and HIV.

Recommended treatment for ophthalmia neonatorum prophylaxis is ocular application of silver nitrate 1% aqueous solution in a single application, erythromycin 0.5% ophthalmic ointment in a single application, or tetracycline ophthalmic ointment (1%) in a single application.

SUMMARY

By culturing for N gonorrhoeae in cases of neonates and children with conjunctivitis, vaginitis, urethritis, proctitis, sepsis, and arthritis, gonococcal infections can be identified easily. They are then treated with ceftriaxone. In neonates, the mother and her sexual contacts also should be treated. In children, a full evaluation for sexual contacts, with tlie assistance of other professionals, if necessary, will almost always identify a sexual contact. Appropriate action then can be taken to protect the child from further sexual contact.

REFERENCES

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15. Ingram DL The gonococcus and the toilet seat revisited, ftdiarr Infect Dis J. 1989;8:191.

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10.3928/0090-4481-19940701-07

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