Meningitis secondary to disseminated gonococcal infection

Abstract

We report one of the unusual presentations of disseminated gonococcal infection. This case report describes a 24-year-old woman who presented with disseminated gonococcal infection manifesting as meningitis. Cerebrospinal fluid (CSF) and throat swab PCR were positive for Neisseria gonorrhoeae. Blood and CSF cultures were negative for bacterial growth. The patient was treated with a total of 14 days of intravenous ceftriaxone. She was discharged with no neurological sequelae.

Background

Disseminated gonococcal infection happens in 0.5%–3% of the patients infected with Neisseria gonorrhoea. Involvement of the central nervous system is a rare manifestation of disseminated gonorrhoea; joints remain the most common site of gonococcal dissemination. This article highlights one of the very few cases of gonococcal meningitis diagnosed with DNA amplification.

Case presentation

The patient is a 24-year-old woman with a history of anxiety and migraines who presented after waking up with a severe headache, different from her usual migraine headaches. Patient reported photophobia and pain radiating down the back of her neck. The patient’s symptoms included myalgias, fatigue, left ankle discomfort, nausea and one episode of emesis. The patient reported having a sore throat and left knee pain which lasted a little over 24 hours, a day prior to admission. Acetaminophen and oxycodone did not provide much relief from her pain. She denied chest pain, shortness of breath, changes in speech or ambulation, dizziness, numbness and history of trauma.

The patient reported being monogamous with a long-term male partner and unprotected sex including oral sex in the 7–10 days prior to symptom onset. Of note, this partner did have a positive chlamydia test approximately 1 month prior, for which the patient received partner treatment with azithromycin. Patient reported using marijuana almost daily.

In the emergency department, the patient was febrile with a maximum temperature of 100.2°F, heart rate of 110 beats/min, blood pressure of 141/88 mm Hg and oxygen saturation of 98% on ambient air. Examination findings included neck stiffness, normal neurological examination with no focal deficits. Cardiovascular, respiratory and abdominal examinations were unremarkable. At the time of initial presentation, there was no joint swelling or tenderness, and no skin rashes were noted. On the second day of hospitalisation, the patient was noted to have left knee effusion.

Differential diagnosis

Based on the patient’s initial clinical presentation, meningoencephalitis was the top differential. Other potential explanations for the patient’s symptoms at time of presentation included an acute migraine episode, cerebrovascular event, intracranial space occupying lesion and substance abuse, all being less likely given the subjective history, lack of neurologic deficits on examination and lab results. Lumbar puncture was done emergently and the cerebrospinal fluid (CSF) evaluation was suggestive of bacterial meningitis. Disseminated gonococcal infection causing meningitis was suspected due to history of associated pharyngitis, ankle and knee arthralgia, left knee effusion and recent history of sexually transmitted infection in her partner. Positive CSF nucleic acid amplification test for N. gonorrhoea established the definitive diagnosis in this patient.

Investigations

At admission, laboratory studies showed mild neutrophilic leukocytosis (white cell count 11.5×10⁹/L), normocytic anaemia (haemoglobin 113 g/L), normal platelet count, elevated aspartate aminotransferase (61 U/L, reference range 0–37 U/L) and elevated alanine aminotransferase (118 U/L, reference range 6–37 U/L). Blood alkaline phosphatase, total protein, albumin, bilirubin, lactic acid, procalcitonin and thyroid stimulating hormone levels were in the reference range.

CSF analysis showed hazy CSF with total nucleated cells of 2401/µL (reference range 0–5/µL) with 85% polymorphonuclear cells, elevated protein (134 mg/dL, reference range 15–45 mg/dL), reduced glucose(38 mg/dL, reference range 50–75 mg/dL), blood glucose of 99 mg/dL (reference range 70–99 mg/dL) and a CSF/blood glucose ratio of 0.38, concerning for bacterial meningitis. No organisms were seen on the gram stain of the CSF specimen. CSF and blood cultures did not yield any bacterial growth. CSF meningoencephalitis PCR panel (Biofire Diagnostics FilmArray system) and venereal disease research laboratory tests were negative. Results of urine pregnancy test, SARS CoV-2 nasopharyngeal swab, HIV screen, acute viral hepatitis panel and serum syphilis IgG were negative. Urinalysis was suggestive of infection and urine culture grew more than 100 000 Col/mL Escherichia coli. Urine drug screen was positive for oxycodone and marijuana which was consistent with the patient’s history.

Given that the initial CSF meningoencephalitis panel was negative for common pathogens, N. gonorrhoeae and Chlamydia trachomatis DNA amplification were performed on the CSF and pharyngeal swab samples. Results returned positive for N. gonorrhoeae in both the CSF and pharyngeal swab specimens. MRI of the brain did not show acute intracranial abnormality. There were incidental findings of mild cerebellar tonsillar ectopia and adenoid hypertrophy (figure 1).

Figure 1.

MRI brain without and with contrast of our patient showing no acute intracranial abnormality. (A) Sagittal T1-weighted scan; (B) axial T2-weighted scan; (C) axial view with fluid attenuated inversion recovery and (D) axial view with gradient echo. A, anterior; I, inferior; L, left; P, posterior; R, right; S, superior.

Treatment and clinical course

Patient was started on empiric therapy for meningoencephalitis including intravenous ceftriaxone, vancomycin, acyclovir and dexamethasone. Two days later, antibiotic regimen was de-escalated to intravenous ceftriaxone alone, after confirmation of gonococcal meningitis. Orthopaedic surgery was consulted to rule out possible septic arthritis in the setting of disseminated gonococcal infection. Owing to the lack of significant joint effusion and improvement of knee pain after several days of empiric intravenous antibiotic therapy, no joint aspiration or other orthopaedic intervention was required. She required opiate medication for control of headache (oxycodone), and she received a prescription for a short course after discharge. The patient was hospitalised for 5 days and discharged with a peripherally inserted central catheter (PICC) to complete 14 days of antibiotics. She was discharged with no apparent neurologic sequelae. Patient was counselled about risks, prevention and treatment of sexually transmitted diseases. Patient notified her partner about the diagnosis and he was treated for presumed gonococcal infection. The local health department was notified.

Outcome and follow-up

One day after discharge, the patient presented with shortness of breath and chest pain exacerbated by moving her left arm. Patient was haemodynamically stable. Chest X-ray showed a left PICC line tip projecting over the right atrium to superior cavoatrial junction. PICC line was retracted by 1 cm with relief of symptoms. One week later, the patient followed up with her primary care provider, and reported gradual resolution of symptoms and decreased need for analgesics. Patient did not have any neurological sequelae noted during follow-up.

Discussion

It is well-known that gonococcus causes urethritis, cervicitis, proctitis, pelvic inflammatory disease, arthritis and pharyngitis but it is also an infrequent cause of meningitis. Disseminated gonococcal infection is a clinical entity characterised by arthritis, tenosynovitis, rash and polyarthralgia, with meningitis being a rare manifestation. Gonococcal meningitis was first reported almost 100 years ago in 1922 and the literature search reveals a little over 20 cases of this clinical entity.

Of the few cases of gonococcal meningitis found in the literature, approximately one-fourth of all cases occurred in previously healthy young adults. It is often seen in patients <40 years of age. Earlier trend showed male preponderance, but this has reversed in recent years.^{1 2} In healthy young adults, the urogenital tract is the most frequent source of infection, but other sites such as the oropharynx may be involved as was the case with our patient.¹

Neurologic manifestations of gonorrhoea have been observed as early as 1805.³ However, the first case of gonococcal meningitis was not documented until 1922.³ Clinical features of meningitis due to gonococcus are no different from meningitis due to other common pathogens. Definite pathogen identification is often delayed in absence of other systemic findings suggesting gonococcal infection.

The Kalamazoo County Health and Community Services Department reported a cluster of 16 cases of disseminated gonococcal infections from 12 August to 18 December 2019. Fourteen of these 16 patients resided in Kalamazoo County; however, there was no definite manifestation of gonococcal meningitis among those cases.⁴

The presence of rash, arthralgia or tenosynovitis on reported history or physical examination point towards possible disseminated gonococcal infection and should prompt healthcare providers to collect diagnostic samples from additional sites such as the rectum, urethra, endocervix, synovial fluid and the oropharynx. In this case, the report of mild arthralgia and knee effusion raised our suspicion for disseminated gonococcal infection.

This patient presented with acute onset of neurological symptoms that started <24 hours prior to admission. It is possible that she was an asymptomatic carrier rather than a newly infected patient leading to the subsequent development of gonococcal meningitis. Given the recent history of unprotected sex and recent genital chlamydia infection in her partner, our patient had risk factors for gonococcal infection. In patients attending sexually transmitted disease clinics with gonorrhoea, median chlamydia positivity was 38.4% in the age group of 15–24 years.⁵

Pharyngeal involvement most commonly happens secondary to orogenital contact, although involvement of pharynx during the process of dissemination from other sites is possible as well. Pharyngeal gonorrhoea is usually asymptomatic and its importance stems from treatment failures associated with this site of infection. Owing to erratic penetration of antibiotics into pharyngeal mucosa, gonococcus lingers for longer duration in the pharynx. The Center for Disease Control recommends test of cure 7–14 days after completing treatment for pharyngeal infection.⁶

Pharyngeal gonorrhoea in our patient was diagnosed based on DNA amplification of throat swab. Even though molecular diagnostic techniques improve the sensitivity, there are pitfalls in their utility at non-genital sites. Pharyngeal mucosa may harbour commensal Neisseria sp, and these may lead to false positive results.⁷

Meningococcus is a far more common cause of meningitis and it is possible that meningitis due to gonococcus could be mistreated as meningococcal meningitis. This is especially true due to their similar appearance on gram stain and overlapping clinical features. Isolation and subsequent identification of gonococcus on culture samples will give more robust diagnostic results. Differentiating these two organisms is important because of the differences in management of close contacts in meningococcal infections and sexual partners in gonococcal infections. It is therefore reasonable to recommend that patients with culture-negative and CSF meningoencephalitis PCR panel-negative initial testing who also have increased probability of gonococcal infection, such as patients with prior infection or high-risk sexual activity, be tested for gonococcal meningitis; there is not currently sufficient evidence to recommend testing all patients with initial culture-negative and PCR panel-negative results for gonococcal meningitis. Further research is needed in the prevalence of gonococcal meningitis prior to making such a recommendation.

Learning points.

• Meningitis is a rare, yet important, manifestation of disseminated gonococcal infection in otherwise healthy, immunocompetent individuals.

• Neisseria gonorrhoeae may be under-recognised as the causal agent of meningitis due to lack of routine testing for N. gonorrhoeae in cerebrospinal fluid.

• Differentiation between Neisseria meningitidis and N. gonorrhoeae meningitis has important implications in regards to treatment, follow-up, and test of cure, and N. gonorrhoeae should be considered in patients with risk factors, including history of sexually transmitted infections.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).