Le Infezioni in Medicina, n. 4, 583-590, 2023

doi: 10.53854/liim-3104-18

CASE REPORTS

Enterococcal meningitis associated with Strongyloides infection: a case report and literature review

Lavinia Cosimi1, Stefano Di Bella2,3, Roberto Luzzati2,3, Catrin Theresia Simeth4, Maurizio Pinamonti5, Franco Cominotto6, Ugo Giulio Sisto6

1Clinical Department of Medical, Surgical and Health Sciences, University of Udine, Italy;

2Clinical Department of Medical, Surgical and Health Science, University of Trieste, Italy;

3Infectious Diseases Unit, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Trieste, Italy;

4Department of Gastroenterology and Digestive Endoscopy, Azienda Sanitaria Univerisitaria Giuliano Isontina (ASUGI), Trieste, Italy;

5Division of Pathology, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Trieste, Italy;

6Department of Emergency Medicine, Azienda Sanitaria Univerisitaria Giuliano Isontina (ASUGI), Trieste, Italy

Received 5 September 2023; accepted 27 October 2023

Corresponding author

Lavinia Cosimi

E-mail: lavinia.cosimi@asugi.sanita.fvg.it;

lavinia.cosimi@live.it

SummaRY

Strongyloides stercoralis is an intestinal nematode endemic throughout tropical and subtropical areas, with a life cycle consisting of free-living and parasitic components. Unlike other soil-transmitted nematodes, it is capable of self-infection, which can cause chronic disease that lasts for decades, or cause overwhelming hyperinfection in people taking corticosteroids or other immunosuppressive drugs or who have impaired Th2 cell-mediated immunity, particularly those infected with human T-lymphotropic virus 1. During hyperinfection, a large numbers of larvae have access to the bloodstream, lungs, central nervous system, and other organs. Bacteremia and polymicrobial meningitis can occur due to disruption of the intestinal mucosa and the presence of bacteria on the surface of foreign larvae.

Enterococcal meningitis for instance may occur concurrently with strongyloidiasis as a consequence of haematogenous dissemination. We present a clinical case of a 45-year-old, man from Bangladesh, in which co-infection occurred. The patient was not immunocompromized and had no apparent risk factors, which represents the unusual aspect of this case report.

A literature review on enterococcal meningitis and Strongyloides coinfection in adult patients was performed encountering 21 cases. Cases have been reviewed and discussed. Clinicians may suspect S. stercoralis co-infection when identifying an enterococcal meningitis in adult patients coming from endemic areas.

Key words: Strongyloides, strongiloydiasis, epidemiology, central nervous system, meningitis, Enterococcus, parasitic disease.

INTRODUCTION

Two species of Strongyloides affect humans: Strongyloides stercoralis and Strongyloides fuelleborni. S. stercoralis has a cosmopolitan distribution in tropical and subtropical regions. In average, healthy individuals, the infection causes relatively little over pathology but may compromise an individual’s nutritional status. S. stercoralis is a soil-­transmitted helminth, classified as a roundworm or nematode. S. stercoralis, commonly known as threadworm, is a soil-transmitted human parasite belonging to a group of nematodes called roundworms. Although prevalent almost worldwide, except only in the far north and south, the global burden of this parasitic infection is still underestimated because of the unavailability of precise data from endemic areas. S. stercoralis, therefore, becomes one of the most overlooked parasitic infections among the “neglected tropical diseases”.

There are more than 50 species of Strongyloides. Most of them do not affect humans. Strongyloidiasis, the disease caused by S. stercoralis in humans, is contracted mainly throughout transcutaneous route. Other modes of transmission include the fecal-oral and anal-oral routes. It can also be transmitted through organ transplantation from an infected donor [1].

However, Strongyloides infection in immunocompromised individuals (particularly following prolonged exposure to corticosteroids or transplant surgery) can result in disseminated strongyloidiasis, in which worms, particularly larvae, move beyond the confines of the gut into other organ [1]. Enterococci are typically commensal species in humans but become pathogenic under specific host conditions. Infections can be acquired in community and nosocomial settings, affecting various areas such as urinary or biliary tracts, surgical sites, endocardium, and meninges [2].

Enterocooccus species is considered as causative agent for urinary tract infections, hepatobiliary sepsis, endocarditis, surgical wound infection, bacteremia, neonatal sepsis, and nosocomial infection with high mortality. Enterococcus faecalis is the most common species associated with clinical infection, while Enterococcus faecium poses the higher antibiotic resistance threat. However enterococci are considered an uncommon causative pathogen for central nervous system infection [2]. Enterococcal meningitis accounts for only 0.3% to 4% of cases of bacterial meningitis which is nevertheless associated with a high mortality rate. It has been described most frequently in patients with neurosurgical conditions (i.e. head trauma, shunt devices, or cerebrospinal fluid leakage), although it can also occur as a “spontaneous” infection complicating remote enterococcal infections such as endocarditis or pyelonephritis [3]. During our clinical practice, we encountered a case of an adult patient in which Strongyloides infection and enterococcal meningitis coexisted in the absence of apparent risk factors for the latter disease. For this reason, we decided to review the literature on this subject to understand the possible pathological mechanisms underlying this co-infection.

CASE REPORT

We present the case of a 45-year-old man from Bangladesh who presented to the emergency department (ED) with complaints of fever (body temperature up to 39°C) and headache. He also reported an unintentional weight loss of 20 kg. His medical history was characterized by a grade 1 meningeal tumor at the level of the left parasellar site (stable and known since 2016). Chest X-ray and head computed tomography (CT) scan were negative, furthermore neurological evaluation showed no pathological signs. Serology for HTLV and HIV resulted negative. Laboratory examinations showed increased values of C-reactive protein (23.4 mg/L, average value <5 mg/L) and white blood cells (20x10/m³). After the following investigations, the patient decides to self-discharge. He then re-attended the ED after four days due to persistent symptoms and new onset nausea, complaining of mild nuchal pain. A lumbar puncture was performed in the ED: the cerebrospinal fluid was cloudy with glucose 41.3 (serum/cerebrospinal fluid ratio 0.4), protein 86 mg/dl, 1559 cells/m³, 70% polymorphonuclear); the multiplex PCR testing for meningitis pathogens (Filmarray meningitis/encephalitis panel, bio­Mèrieux, Italy) was negative. A new head CT scan was unremarkable. The patient was then admitted to the Infectious Diseases ward and started on empirical therapy with intravenous ceftriaxone 2 g every 12 hours, acyclovir and dexamethasone 10 mg every 6 hours (continued for 11 days). Ampicillin was not added since the patient had no risk factors for Listeria monocytogenes. Despite the antibiotic therapy, the patient did not improve, and a second lumbar puncture was then performed. The culture of cerebrospinal fluid resulted positive for E. faecalis (fully susceptible to the tested antimicrobials), and a targeted therapy with ampicillin 4 g every 6 hours was added to the previous therapy with ceftriaxone 2 g every 12 hours. Acyclovir was then discontinued. A marked and rapid improvement of headache was observed, and concomitant resolution of rigor nucalis after 48 hours/days. Since normocytic anemia (hemoglobin was 8,8 g/deciliter) with a positive fecal occult blood test was detected during hospitalization, he underwent an urgent colonoscopy, which revealed edematous mucosa and the presence of small aphthous ulcers. throughout the colon (Figure 1).

Figure 1 - Image of the colonoscopy- mucosal edema and aphthous ulcers along the colon.

The parasitological examination of S. stercoralis was confirmed by stool specimen examination, and the histological examination confirmed the diagnosis of parasitosis. Histological examination showed typical mucosal architecture with a diffuse inflammatory infiltrate consisting mainly of lymphocytes and plasma cells with a fair number of eosinophilic granulocytes. The eosinophils tended to cluster around the crypts, showing focal aspects of pericryptosis. Some non-necrotizing epithelioid microgranulomas were also present in the lamina propria. Some crypts harbored corpuscles morphologically compatible with parasites (Figure 2). Therefore, treatment with ivermectin 15 mg was undertaken with a first dose of the drug repeated one week apart.

Figure 2 - a) Histology of the colon mucosa. haematoxylin and eosin (H&E), original magnification x 200. Three parasites are visible within the intestinal crypts. The lamina propria shows a polymorphous inflammatory infiltrate containing numerous eosinophils; b) - Histology of the colon mucosa. H&E, original magnification x 200. The lamina propria shows a moderate inflammatory infiltrate including numerous eosinophils and a small granuloma in formation.

The antibiotic therapy lasted 18 days, gradually improving patient health conditions. He was then discharged and followed later by the outpatient service. No relapse events were reported up to 30 days following his discharge.

LITERATURE REVIEW

We performed a literature review of Strongyloides stercoralis and enterococci co-infections in either immunocompetent or immunocompromised patients population. In May 2023, we searched PubMed using the following search strings: “MENINGITIS” AND “ENTEROCOCCUS”. Overall 325 articles on this topic were identified. From these, we selected 27 articles in which the co-infection of S. stercoralis and enterococci was considered. Cases in which there was no microbiological isolation on CSF culture and, therefore no definite diagnosis of enterococcal meningitis were also included in the review. The paediatric population was not taken into consideration. Above all the 27 articles, 6 were excluded for unavailability of an English or Italian version, overall resulting in 21 papers included in the analysis. Inclusion and exclusion criteria are illustrated in the flow-chart reported below.

The cases of S. stercoralis and enterococci co-infections reported in the literature (Table 1) include mainly immunocompromised subjects; only 1 patient has no relevant pathological history. Alcoholism, HIV and HTLV-1 infection, hematologic malignancies, post-transplant status, and other immunocompromising therapies are known risk factors for persistent S. stercoralis infection and also increase the risk of hyperinfection syndrome and disseminated strongyloidiasis. Many of the patients appear to have been exposed to prolonged corticosteroid treatment prior to hospitalization due to infection-related symptoms, which could be considered as an additional risk factor. A higher frequency of SEC is also observed in male than female subjects.

In many 15 of the cases mentioned, data on the chemical-physical characteristics of the cerebrospinal fluid were not reported. Among the cases mentioned, 13 of them were found to be positive to culture isolations (blood cultures; CSF) for enterococci, attesting to the invasiveness of the infection by this etiological agent. Almost all reported cases are characterized by the identification of S. stercoralis through culture, microscopic, or histological testing. Unfortunately, 12 of the reported cases result in early death despite timely administration of broad-spectrum antibiotic therapy.

Table 1 - Cases reported in the literature of enterococcal meningitis associated with infection with Strongyloides. (CSF: cerebrospinal fluid; CLD: chronic liver disease; HTLV-1: human t-lymphotropic virus; COPD: chronic obstructive pulmonary disease; HBV: hepatitis B virus).

DISCUSSION

Strongyloidiasis has been recently considered a neglected tropical disease by the World Health Organization due to its global distribution and high burden all over the world. Since the parasite can be continuously auto-infecting the host, many patients remain asymptomatic or have mild symptoms for decades, even after leaving the endemic area and going unnoticed. Rhabditiform larvae are excreted in the stools of infected individuals and can develop into infective filariform larvae in warm, moist soil, which can pierce intact skin and affect a new host, invade the lungs via the bloodstream, migrate to the small intestine to settle, reach maturity, and replicate. S. stercoralis has two ways of auto-infection: the rhabditiform larvae develop into filariform larvae and then enter the bloodstream from the intestine, or they do not develop into filariform larvae but enter the bloodstream directly from the intestinal mucosa (endo auto-infection) [4].

The clinical presentation of strongyloidiasis is variable in terms of both symptoms and severity. Strongyloidiasis can be acute, chronic, persistent, or severe disseminated infection, which can involve multiple organs [19-21]. The enteric bacteria are also carried by invasive larvae on their outer surfaces, this can result in septicemia and in meningitis, which represent a disseminated bacterial infection. Disseminated disease is characterized by the presence of parasites in organs outside the traditional life cycle sites, such as the central nervous system (Figure 3) [8, 9].

Figure 3 - Disseminated strongyloidiasis is characterized by diffusion of gut flora into the bloodstream, leading to bacteremia.

An analysis of the cases reported by the literature result that most of them are characterised by a relevant clinical history: only two of the reported cases did not show a clinical history suggestive of immunosuppression. This aspect reinforces the peculiarity of this clinical case suggesting the hypothesis of investigating the presence of a co-infection in those cases where intestinal translocation is suspected. The presence of a chronic strongyloidiasis could intercur when a diagnosis of enterococcal meningitis is carried-out by clinicians. The presence of S. stercoralis infection in fact may predispose immunocompromised population as either patients presenting just the epidemiological criterion without other apparent risks factors.

REFERENCES

  1. Mora Carpio AL, Meseeha M. Strongyloides stercoralis. StatPearls. Treasure Island, Fla: StatPearls Publishing; 2022. Available at: https://www.ncbi.nlm.nih.gov/books/NBK436024/ (accessed 31.08.2023).
  2. Moellering RC Jr. Emergence of Enterococcus as a significant pathogen. Clin Infect Dis. 1992; 14 (6): 1173-1176. doi: 10.1093/clinids/14.6.1173.
  3. IIaria C, Stassi G, Costa GB, Di Leo R, Toscano A, Cascio A. Enterococcal meningitis caused by Enterococcus casseliflavus. First case report. BMC Infect Dis. 2005; 5 (1): 3. doi: 10.1186/1471-2334-5-3.
  4. Wee LE, Hnin SWK, Xu Z, Lee LS. Strongyloides hyperinfection associated with Enterococcus faecalis bacteremia, meningitis, ventriculitis and gas-forming spondylodiscitis: a case report. Trop Med Infect Dis. 2020; 5 (1): 44. doi: 10.3390/tropicalmed5010044.
  5. Zeana C, Kubin CJ, Della-Latta P, Hammer SM. Vancomycin-resistant Enterococcus faecium meningitis successfully managed with linezolid: case report and review of the literature. Clin Infect Dis. 2001; 33 (4): 477-482. doi: 10.1086/321896.
  6. Tobin MA, Dougherty DF, Ratliff PD, Judd WR. Combination therapy for disseminated strongyloidiasis with associated vancomycin-resistant, linezolid-intermediate Enterococcus faecium meningitis: A case report. J Clin Pharm Ther. 2022; 47 (1): 121-124. doi: 10.1111/jcpt.13448.
  7. Schein F, Fouillet L, Lutz MF, Daguenet E, Botelho-Nevers E, Cornillon J. Recurrent Enterococcus faecalis meningitis in a patient presenting with Strongyloides hyperinfection syndrome during HTLV-1-induced T-cell lymphoma. Med Mal Infect. 2018; 48 (6): 428-430. doi: 10.1016/j.medmal.2018.04.389.
  8. Shrestha P, O’Neil SE, Taylor BS, Bode-Omoleye O, Anstead GM. Hemoptysis in the immunocompromised patient: do not forget strongyloidiasis. Trop Med Infect Dis. 2019; 4 (1): 35. doi: 10.3390/tropicalmed4010035.
  9. Einsiedel L, Fernandes L. Strongyloides stercoralis: a cause of morbidity and mortality for indigenous people in Central Australia. Intern Med J. 2008; 38 (9): 697-703. doi: 10.1111/j.1445-5994.2008.01775.x.
  10. Bamias G, Toskas A, Psychogiou M, et al. Strongyloides hyperinfection syndrome presenting as enterococcal meningitis in a low-endemicity area. Virulence. 2010; 1 (5): 468-470. doi:10.4161/viru.1.5.12703.
  11. Link K, Orenstein R. Bacterial complications of strongyloidiasis: Streptococcus bovis meningitis. South Med J. 1999; 92 (7): 728-731. doi: 10.1097/00007611-199907000-00016.
  12. Somin M, Neogolani V, Zimhony O, Wolpart A, Sokolowski N, Malnick S. Fatal recurrent bacterial meningitis: a complication of chronic Strongyloides infection. Eur J Intern Med. 2008; 19 (6): e42-43. doi: 10.1016/j.ejim.2007.07.009.
  13. Ortega-Díaz M, Puerta Carretero M, Martín Navarro JA, et al, Immunosuppression as a trigger for hyperinflammatory syndrome due to Strongyloides stercoralis in membranous nephropathy. Nefrologia (Engl Ed). 2020; 40 (3): 345-350. doi: 10.1016/j.nefro.2019.04.007.
  14. Sugiura A, Fujimoto M, Saida Y. Enterococcal meningitis due to Strongyloidiasis with HTLV-1 carrier. Rinsho Shinkeigaku. 2006; 46 (10): 715-717.
  15. Khadka P, Khadka P, Thapaliya J, Karkee DB. Fatal strongyloidiasis after corticosteroid therapy for presumed chronic obstructive pulmonary disease. JMM Case Rep. 2018; 5 (9): e005165. doi: 10.1099/jmmcr.0.005165.
  16. Sahu KK, Mahagaokar K, Patel B, et al. Strongyloides stercoralis hyperinfection syndrome in mantle cell lymphoma in post-transplant setting. Ann Hematol. 2021; 100 (4): 1089-1091. doi: 10.1007/s00277-020-04049-8.
  17. Zahar JR, Tankovic J, Catherinot E, Meshaka P, Nitenberg G. Méningite à Enterococcus faecalis au cours d’une anguillulose. Presse Med. 2006; 35 (1 Pt 1): 64-66. doi: 10.1016/s0755-4982(06)74523-7.
  18. Panosian KJ, Marone P, Edberg SC. Elucidation of Strongyloides stercoralis by bacterial-colony displacement. J Clin Microbiol. 1986; 24 (1): 86-88. doi: 10.1128/jcm.24.1.86-88.1986.
  19. Marcos LA, Terashima A, Dupont HL, Gotuzzo E. Strongyloides hyperinfection syndrome: an emerging global infectious disease. Trans R Soc Trop Med Hyg. 2008; 102 (4): 314-318. doi: 10.1016/j.trstmh.2008.01.020.
  20. Ashiri A, Beiromvand M, Khanzadeh A. Strongyloides stercoralis infection in a patient with rheumatoid arthritis and type 2 diabetes mellitus: a case-based review. Clin Rheumatol. 2019; 38 (11): 3093-3098. doi: 10.1007/s10067-019-04611-4.
  21. Bhasin A, Yura E, Boyd D, Kuksuk L, Flaherty JP. Case Report: Incidentally discovered Strongyloides stercoralis infection after urinary diversion. Am J Trop Med Hyg. 2020; 102 (6): 1396-1398. doi: 10.4269/ajtmh.19-0956.
  22. Oktar N, Ozer HM, Demirtas E. Central Nervous System Strongyloides stercoralis. A Case Report. Turk Neurosurg. 2020; 30 (5): 776-779. doi: 10.5137/1019-5149.JTN.22886-18.2.
  23. Ganesh S, Cruz RJ Jr. Strongyloidiasis: a multifaceted disease. Gastroenterol Hepatol. (N Y). 2011; 7 (3): 194-196.
  24. Afzal A. Siddiqui, Steven L. Berk, Diagnosis of Strongyloides stercoralis infection, Clin Infect Dis. 2001; 33 (7): 1040-1047.
  25. Grover IS, Davila R, Subramony C, Daram SR. Strongyloides infection in a cardiac transplant recipient: making a case for pretransplantation screening and treatment. Gastroenterol Hepatol (N Y). 2011; 7 (11): 763-766.
  26. Kassalik M, Mönkemüller K. Strongyloides stercoralis hyperinfection syndrome and disseminated disease. Gastroenterol Hepatol (N Y). 2011; 7 (11): 766-768.