A case of ehrlichiosis with meningoencephalitis and multi-organ failure

Abstract

Ehrlichiosis is a bacterial illness primarily transmitted through the bite of an infected lone star tick. According to the Centers for Disease Control (CDC), the United States is experiencing a rising number of reported cases, with a case fatality rate of approximately 1 %. The disease typically manifests as a non-specific flu-like illness, however in rare cases, it can progress to severe disease with multi-organ failure and mortality. We present a case of a 70-year-old male who was transferred to the intensive care unit of our facility for the management of septic shock associated with multi-organ failure. He had a history of recent exposure to multiple tick-bites while performing yard work. He was diagnosed with Ehrlichiosis based on positive serum IgM and IgG antibodies against Ehrlichia chaffeenesis. A lumbar puncture also confirmed meningoencephalitis. The patient completed intravenous Doxycycline treatment for 14 days, resulting in clinical improvement. Identifying Ehrlichia as the causal organism for meningoencephalitis and severe disease is challenging due to its low prevalence. This case emphasizes the significance of promptly suspecting and identifying ehrlichiosis in patients who exhibit meningoencephalitis symptoms or end-organ failure and have a recent history of engaging in outdoor activities with a risk of exposure to ticks, especially in endemic regions. It also signifies the importance of empirically treating with doxycycline even before its diagnosis as delay in providing doxycycline can significantly lead to more complications compared with patients who receive it early on during hospital admission.

Introduction

Ehrlichia chaffeenesis is a gram-negative obligate intracellular bacterium primarily transmitted through the bite of an infected lone star tick (Amblyomma Americanum), which is predominantly found in the south-central and eastern United States. Ehrlichiosis was first recognized in the US in the 1980s and became a reportable disease in 1999. Since then, there has been a gradual increase in reported cases [1]. Ehrlichiosis usually manifests as mild to moderate flu-like illness, however in rare cases, it can manifest as a severe disease with multi-organ failure that might lead to death if not treated properly. Limited reports exist describing Ehrlichia meningoencephalitis, its prognosis or management.

Case presentation

This is a case of a 70-year-old male residing in Georgia, USA who has a medical history of coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease, and obstructive sleep apnea. He was transferred to the Intensive Care Unit (ICU) from another facility due to septic shock and multi-organ failure.

The patient presented with symptoms of fever, generalized weakness, and cough that progressed over a span of three weeks to shortness of breath, confusion, and hallucinations. The family reported that he frequently engaged in outdoor activities such as yard work, and was exposed to several tick bites. On physical examination, he was noted to be hypoxic, tachycardic, tachypneic, and confused. He had left knee ecchymosis as well as a petechial rash of the lower extremities. No ticks were identified on skin assessment. Initial laboratory testing revealed leukopenia and thrombocytopenia, along with acute kidney injury and transaminitis as outlined in Table 1. CT scan showed bilateral pleural effusions; therefore, he was initially diagnosed with severe sepsis secondary to community-acquired pneumonia.

Table 1.

Laboratory investigations on separate days during hospitalization.

Laboratory studies		Day 1	Day 5	On discharge	Normal Range
Complete blood count	White blood cell count	3.2	17.5	4.1	4.00–10.50 10 * 3/µL
	Hemoglobin	14.5	7.1	7.4	13.8–17.2 g/dL
	Platelets	66	189	242	130–400 10 * 3/µL
Coagulation studies	Prothrombin time	15.4	29.1	13	9.4–12.5 Secs
	International normalized ratio	1.2	2.55	1.1	0.90–1.20
	Activated Partial Thromboplastin Time	53	31.4	31.4	23.8 – 37.9 Secs
Complete metabolic panel	Sodium	125	138	132	133–145 mmol/L
	Potassium	4	5.8	3.9	3.3–5.1 mmol/L
	Calcium	8.3	5.1	8.6	8.4–10.2 mg/dL
	Chloride	91	103	97	98–108 mmol/L
	Bicarbonate	21	17	25	22–32 mmol/L
	Blood urea nitrogen	41	105	51	6–20 mg/dL
	Creatinine	1.6	6.6	5.3	0.50–1.20 mg/dL
	Glomerular filtration rate	46 %	8	11	> =60 mL/min/1.73sq m
	Aspartate transaminase	151	1119	17	12–50 U/L
	Alanine transaminase	38	87	7	7–52 U/L
	Alkaline phosphatase	65	184	75	32–126 U/L
	Total bilirubin	0.8	0.7	0.6	0.2–1.4 mg/dL
	Albumin	3.7	1.7	2.3	3.0–5.0 g/dL

Despite receiving appropriate resuscitation and broad-spectrum antibiotics including vancomycin and piperacillin-tazobactam; his hospital stay was complicated by the development of acute respiratory failure, which necessitated intubation. Additionally, he experienced acute renal failure, for which continuous renal replacement therapy (CRRT) was required. He also developed transaminitis and disseminated intravascular coagulation (DIC). Although there was a growing concern for meningitis, lumbar puncture was postponed due to DIC and increased risk of bleeding.

After the aforementioned complications, there was a growing concern for tick-borne infections, therefore Doxycycline was added on the fourth day of hospitalization. He was then transferred to our facility for a higher level of critical care.

The initiation of doxycycline led to significant clinical improvement and the patient started to recover. A lumbar puncture was performed following the resolution of thrombocytopenia, which was on the tenth day of the hospital stay. Although it was traumatic with bloody CSF, CSF analysis suggested meningoencephalitis, with predominant neutrophils in addition to elevated protein, results are summarized in Table 2. CSF was also tested for common pathogens, as described in Table 3. Blood and CSF cultures were all negative.

Table 2.

Results of CSF Analysis.

Glucose	202 mg/dL
Protein	> 200 mg/dL
Nucleated cells	95 / mm3
RBCs	92,646 / mm3
Neutrophils	76 %
Lymphocytes	17 %
Basophils	2 %
Monocytes	1 %

Table 3.

CSF Analysis; Meningitis/Encephalitis common pathogens tested by PCR.

Pathogen	Result
Escherichia coli K1	Not detected
Haemophilus influenzae	Not detected
Listeria monocytogenes	Not detected
Neisseria meningitidis	Not detected
Streptococcus agalactiae	Not detected
Streptococcus pneumoniae	Not detected
Cytomegalovirus (CMV)	Not detected
Enterovirus	Not detected
Herpes Simplex Virus 1 (HSV−1)	Not detected
Herpes Simplex Virus 2 (HSV−2)	Not detected
Human Herpesvirus 6 (HHV−6)	Not detected
Human Parechovirus	Not detected
Varicella Zoster Virus	Not detected
Cryptococcus neoformans/gattii	Not detected

Tick-borne serologies were ordered by testing serum for the presence of antibodies against Rocky Mountain Spotted Fever, Lyme disease, Ehrlichia, and Anaplasma phagocytophilum. The Ehrlichia antibody panel was the only test that showed positive results for both IgM and IgG (Table 4), supporting a diagnosis of Ehrlichiosis. A peripheral blood smear was examined on a sample drawn 2 days after initiation of doxycycline, and it was negative for any intracytoplasmic inclusions.

Table 4.

Serodiagnostic evaluation of Ehrlichia.

Serological testing		Antibody titer
Ehrlichia chaffeensis	IgM	1:40
	IgG	1:256
Anaplasma phagocytophilum	IgM	< 1:20
	IgG	< 1:64

Intravenous Doxycycline treatment was continued for fourteen days, administered at 100 mg twice daily, and other antimicrobials were discontinued. Although the patient had significant clinical improvement, he had persistent moderate cognitive deficits as well as expressive and receptive aphasia upon discharge. His acute renal failure was attributed to acute tubular necrosis necessitating intermittent hemodialysis after discharge. He also developed complications of his prolonged critical illness including occipital and sacral decubitus ulcers. He was discharged to a rehabilitation facility after 28 days of hospitalization.

A diagnosis of Ehrlichiosis with meningoencephalitis was established based on the patient’s marked clinical improvement following the initiation of doxycycline, positive Ehrlichia antibody titers, CSF findings showing elevated protein and neutrophilic predominance, and negative results from other diagnostic tests.

Discussion

Ehrlichiosis usually manifests as mild to moderate flu-like illness, with symptoms including fever, chills, fatigue, and headache that can be attributed to common viral etiologies [2]. The bacteria can spread through the body via the mononuclear phagocytic system and can affect numerous organs such as the brain meninges, lungs, or kidneys [3]. Therefore, it can progress to severe disease with multi-organ failure and possibly death. This happens in rare cases, with risk factors that include older age, immunocompromise, or delay in treatment with doxycycline [4].

The diagnosis of ehrlichiosis can be established through several diagnostic modalities, including peripheral blood smear evaluation for the presence of intracytoplasmic inclusions (morulae), molecular testing via PCR, in vitro cultivation, and serological testing. The most sensitive method for confirming the diagnosis is through demonstrating seroconversion or a fourfold increase in antibody titers between the acute and convalescent phases. This approach has a sensitivity exceeding 90 % when the tick-bite is suspected to have occurred more than three weeks prior [5]. Our patient, whose initial symptoms started over 3 weeks prior, demonstrated positive antibody titers, along with a clinical presentation strongly suggestive of Ehrlichiosis and significant improvement after initiating doxycycline, leading to the establishment of the diagnosis. Although the peripheral blood smear evaluation was negative for morulae, this test has low sensitivity, and initiating treatment with doxycycline highly affects the likelihood of detecting morulae on blood smear examination [5].

The lumbar puncture was noted to be traumatic which could explain the elevated nucleated cells, however, the presence of elevated protein indicated an abnormal CSF profile concerning for CNS infection. A study reviewing CSF findings in patients with Ehrlichiosis and CNS involvement reported lymphocytic pleocytosis and elevated protein as the most common abnormalities [6]. Other differential diagnoses considered included West Nile virus, Zika virus, and dengue virus, as they are known causes of tick-borne viral encephalitis. However, these were not tested due to low clinical utility since the patient showed marked clinical improvement after initiating doxycycline, which would be unlikely in viral infections.

Ideally, antibody titers should have been repeated after the resolution of the acute phase to confirm the diagnosis; however, this was not performed due to the patient's lack of follow-up, representing a limitation in our case. Nonetheless, Ehrlichiosis remains the most probable diagnosis given the patient’s clinical presentation and marked improvement following doxycycline therapy.

Our patient had multiple medical co-morbidities and did not receive doxycycline in a timely manner, which predisposed him to progress to severe disease with multi-organ failure. According to a study done by Hamburg et al., delay in providing doxycycline significantly led to more complications including respiratory complications, mechanical ventilation, and ICU admission compared with patients who received doxycycline within the first 24 hours of admission to the hospital [4].

Multiple factors make diagnosing ehrlichiosis challenging. First, the non-specific clinical and laboratory manifestations of ehrlichiosis make other common etiologies to be prioritized. Second, Ehrlichia is an obligate intracellular bacterium that grows within membrane-bound vacuoles in human and animal leukocytes, and it does not grow in standard medium, therefore, it will be challenging to identify it through routine hospital blood cultures. In addition, factors like unavailable Infectious Disease specialists in the facility and lack of expertise are likely to delay diagnosis [7].

Limited cases are reported in the literature about Ehrlichia meningoencephalitis, with doxycycline being the mainstay of treatment in available cases. No alternative antibiotic regimens were reported for comparison with the intervention used in our described case.

Physicians must have high clinical suspicion for tick-borne disease in endemic areas, especially in patients who report outdoor activities and non-specific symptoms. Early administration of doxycycline is essential due to the risk of rapid progression to severe disease without treatment.

The limited available literature on Ehrlichia meningoencephalitis highlights its rare occurrence and emphasizes the necessity for additional data to enhance our understanding of its long-term prognosis. We believe our case will help contribute to the paucity of literature regarding this condition and its severe complications.

Author Contributions

Dr Neaam Al-Bahadili conceived the idea of the case report, collected clinical data, and drafted the case description and discussion. Dr Ibrahim Shamasneh and Dr Chinelo Meniru contributed to the literature review, critical revision, as well as writing the abstract, introduction, and conclusion. Dr Zola Nlandu contributed to supervising the manuscript write up and ensuring medical and clinical accuracy.

Ethical Compliance

Verbal informed consent was obtained from the patient for the publication of this case report and accompanying data. This report adheres to ethical guidelines and institutional policies.

Funding

No funding was received for this case report.

CRediT authorship contribution statement

Al-Bahadili Neaam: Writing – review & editing, Writing – original draft, Conceptualization. Nlandu Zola: Writing – review & editing, Supervision. Meniru Chinelo: Writing – original draft. Shamasneh Ibrahim: Writing – review & editing, Writing – original draft, Conceptualization.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.