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Case of the Month

October 2019

Case report- LO1 (Helderberg Hospital)

Case courtesy of: Drs Dawood da Costa1, Rena Hoffmanna1, Wiedaad Pietersen2
  1. Department of Medical Microbiology and Immunology, Tygerberg Hospital, Cape Town, National Health Laboratory Service
  2. Department of Internal Medicine, Helderberg Hospital, Somerset West, Cape Town
Written consent was obtained from the patient to publish images.

A 61-year-old male presented to the emergency department at Helderberg Hospital, Cape Town, with a 4-day history of headaches, fever, malaise, loss of appetite and a 1-day history of photophobia and confusion. Collateral history obtained in the emergency unit reported no history of vomiting, cough, night sweats, loss of weight, trauma or preceding upper respiratory tract infection symptoms.

His medical history included HIV infection diagnosed 5 years previously, and he was on a fixed dose combination of tenofovir 300mg, emtricitabine 200mg, and efavirenz 600mg antiretroviral therapy (ART). His most recent CD4 count was 330 cells/ul in May 2017, and HIV viral load (6 months before presentation, in May 2018) was less than 50 copies/ml. He had no previous TB history, no known recent household TB contact, and no recent travel history. He is a non-smoker, does not drink alcohol and adherent to his ART.

He is self-employed as a livestock farmer with pigs, goats and sheep. During the admission it was noted that he had a history of a pig bite 10 days before presentation.

On admission he was febrile with a temperature of 38.6°C, tachycardic with a pulse of 112 bpm, normotensive with a blood pressure of 106/67 mm Hg and a fingerprick glucose test: 6.4mmol/l. He was disorientated to time, place and person with a Glasgow Coma Score of 14/15. He had evidence of a healing bite wound on his left thumb with no evidence of wound sepsis (see Figure 1). He had no evidence of anaemia, clubbing or lymphadenopathy.

Clinically, he had meningism with neck stiffness, and no focal neurological signs. He had no evidence of a skin rash, or stigmata of infective endocarditis.

His respiratory, abdominal, cardiac and neurological examination was otherwise unremarkable.

His chest x-ray was normal. Urine dipstix was normal, and bloods were drawn.

A CT brain was not performed. He was initiated on high-dose ceftriaxone 2g intravenously and admitted.

Which tests would you consider appropriate for this patient?

  1. Sterile blood culture: 1 aerobic blood culture and 1 anaerobic blood culture inoculated with a minimum of 10 ml blood in each blood culture bottle.
  2. Bloods: Full blood count; urea, electrolytes and creatinine; C-reactive protein; liver function tests; syphilis serology
  3. Lumbar puncture:
    1. Measurement of cerebrospinal fluid (CSF) opening pressure and visualisation of CSF turbidity.
    2. Routine microscopy (Gram stain), routine bacterial culture and antibiotic susceptibility testing.
    3. TB testing: GeneXpert Ultra; TB microscopy, culture and sensitivity. GeneXpert Ultra has improved sensitivity for MTB complex detection.
    4. India ink stain: to look for the presence of encapsulated yeasts in suspected cryptococcal meningitis.
    5. Cryptococcal antigen testing: the cryptococcal antigen lateral flow assay6 has a sensitivity and specificity of 100% for detection of Cryptococcus neoformans in patients with cryptococcal meningitis.
    6. Syphilis serology: treponemal-detection test: FTA-Ab, non-treponemal detection test: VDRL
  4. Respiratory sample testing (sputum; induced sputum): TB testing if deemed clinically necessary.
  5. Tissue sample: routine microscopy, culture and susceptibility testing if evidence of skin and soft tissue infection.

What is the differential diagnosis in a person with HIV disease with history and clinical features suggestive of community-acquired meningitis?

  1. Acute bacterial meningitis:
    1. Streptococcus pneumoniae meningitis (Gram positive cocci/lancet-shaped diplococci)
    2. Listeria monocytogenes meningitis (small, Gram positive bacilli)
    3. TB meningitis
    4. Owing to the bite history, consider zoonosis with oral flora of pigs: these include Staphylococcus species, Streptococcus species, Pasteurellae species and anaerobic organisms (with associated brain abscess)
  2. Acute viral meningitis: Herpesviruses (HSV1, HSV2, CMV, EBV, VZV, HHV6), mumps, enterovirus.
  3. Sub-acute meningitis a. TB meningitis b. Cryptococcal meningitis

What is the differential diagnosis in a person with HIV disease with history and clinical features suggestive of community-acquired meningitis?

  1. Acute bacterial meningitis:
    1. Streptococcus pneumoniae meningitis (Gram positive cocci/lancet-shaped diplococci)
    2. Listeria monocytogenes meningitis (small, Gram positive bacilli)
    3. TB meningitis
    4. Owing to the bite history, consider zoonosis with oral flora of pigs: these include Staphylococcus species, Streptococcus species, Pasteurellae species and anaerobic organisms (with associated brain abscess)
  2. Acute viral meningitis: Herpesviruses (HSV1, HSV2, CMV, EBV, VZV, HHV6), mumps, enterovirus.
  3. Sub-acute meningitis
    1. TB meningitis
    2. Cryptococcal meningitis

In this patient:

  1. He was admitted to the ward and intravenous high-dose ceftriaxone 2g 12 hourly intravenously was initiated.
  2. On agar plated CSF and blood culture broth, blood agar growth consisting of 2-3mm round, smooth, translucent colonies with small zones of beta-haemolysis was noted on day 1 (see Figure 3). It did not grow on bile-aesculin agar, and was susceptible to all antibiotics tested (cefotaxime, clindamycin, erythromycin, vancomycin) by Kirby-Bauer disk-diffusion method. Penicillin gradient diffusion testing had a MIC of 0.047µg/ml (see Figure 4). Antimicrobial susceptibility testing was interpreted according to CLSI criteria for zone diameter and MIC breakpoints for Streptococcus spp β-haemolytic group. The cultured isolate did not type for Lancefield grouping by latex agglutination streptococcaltyping (Avipath Strep, Omega Diagnostics). Automated Vitek 2 testing (GP ID card, Biomerieux) on both blood culture and CSF culture isolate identified Streptococcus suis I. Molecular 16S rRNA PCR sequencing confirmed S. suis.
What is Streptococcus suis?
S. suis is a Gram-positive coccus forming part of the oropharyngeal microbiota of pigs and is common in their tonsils and nares. It is an opportunistic pathogen causing meningitis, arthritis, endocarditis, and spontaneous abortion in pigs. It is a zoonotic organism, and in humans it is most commonly associated with meningitis (60-70%), septicaemia, arthritis, endocarditis and endophthalmitis and has been associated with outbreaks.

How common is it and who is at risk?
Globally, there have been less than 2000 reported cases of S. suis infection. Significant risk factors are occupational exposure; eating undercooked, contaminated food; skin and soft-tissue injury; and underlying illness. A recent meta-analysis reported a pooled case-fatality rate of 12,5% in infected patients. Hearing loss or vestibular dysfunction are common sequelae, occurring in up to 50% of patients with meningitis.

How is it diagnosed?
Most cases of S. suis are diagnosed on blood or cerebrospinal fluid culture. Misdiagnosis is not uncommon, with misidentification as viridans streptococci occurring in between 20-70% of confirmed S. suis cases with both biochemical and automated testing methods.

How is it managed?
S. suis cases reported in the literature are generally susceptible to penicillin, with only two cases of penicillin resistance reported. Intravenous beta-lactam therapy for 2 weeks is the recommended treatment. There are no studies assessing optimum duration of therapy. Clinicians should be cognizant and screen for post-meningitis auditory and vestibular dysfunction.

What was this patient’s clinical course and management?
This patient was treated with intravenous ceftriaxone 2g 12 hourly.
He was afebrile, fully orientated and free of headaches and neck stiffness within 48 hours of therapy. During the second week of therapy, he developed herpes zoster on his neck which was treated with and responded well to oral acyclovir therapy.
He was discharged to continue lifelong antiretroviral therapy.
Three months after discharge, he had a formal hearing test with a normal audiogram result.
No further investigation was performed in the pig herd.

References:

  1. Huong VTL, Ha N, Huy NT, Horby P, Nghia HDT, Thiem VD, et al. Epidemiology, clinical manifestations, and outcomes of streptococcus suis infection in humans. Emerg Infect Dis.

    2014;20(7):1105–14.

  2. Haas B, Grenier D. Understanding the virulence of Streptococcus suis: A veterinary, medical, and economic challenge. Med Mal Infect [Internet]. 2018;48(3):159–66. Available from: https://doi.org/10.1016/j.medmal.2017.10.001
  3. Murase K, Watanabe T, Arai S, Kim H, Tohya M, Ishida-Kuroki K, et al. Characterization of pig saliva as the major natural habitat of Streptococcus suis by analyzing oral, fecal, vaginal, and environmental microbiota. PLoS One. 2019;14(4):1–17.
  4. Yongkiettrakul S, Maneerat K, Arechanajan B, Malila Y, Srimanote P, Gottschalk M, et al. Antimicrobial susceptibility of Streptococcus suis isolated from diseased pigs, asymptomatic pigs, and human patients in Thailand. BMC Vet Res. 2019;15(1):1–12.
  5. Mandell, Douglas, and Bennett’s. Principles and Practice of Infectious Diseases 8th Edition.

    Chapter 204; 2360

  6. Cryptococcal antigen lateral flow assay, CrAg® LFA, Package insert. IMMY.
  7. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 29TH ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2019.

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