CASE

A 74 year-old Portuguese speaking man with history of hypertension, hyperlipidemia, depression, non-insulin-dependent diabetes, presented to the emergency department with one week of left flank pain. The pain was gradual in onset and cramping in quality. The pain was constant and worse since beginning last week, approaching 10/10 in severity. It was located over the left flank and radiated toward the left abdomen and groin. The patient stated his symptoms began while cooking dinner. He had been working in his home vineyard and vegetable garden all day.

The patient does not recall any recent traumatic event. He had never had this type of pain before. The patient had been taking ibuprofen and acetaminophen for his symptoms, both of which had helped only minimally. The patient stated that the pain was worse with exertion or movement of any kind. He had not traveled recently and had no sick contacts. In addition to the flank pain, the patient endorsed subjective low-grade fevers, as well as a lack of appetite and mild nausea. Review of systems was negative for vomiting, chest pain, shortness of breath, cough, congestion, rash, weight loss, night sweats, leg swelling, dysuria, hematuria, diarrhea, hematochezia, constipation, or melena.

The patient smoked one pack of cigarettes per day, and drank several glasses of wine per night. He denied any drug use. He lived with his wife and was a retired plumber. He enjoyed gardening, watching soccer, and caring for his grandchildren.

His past surgical history was significant for a prior inguinal hernia repair, and there was a history of coronary artery disease in his siblings. His current medications included amlodipine, atorvastatic, hydralazine, lisinopril, metformin, and sertraline.

Vital signs showed a blood pressure of 110/65, heart rate of 104, temperature of 100.5 F, a respiratory rate of 18, and an oxygen saturation of 95% on room air. On physical exam:

General: Awake, alert, diaphoretic, uncomfortable appearing

HEENT: MMM, no icterus, normal oropharynx

Neck: No JVD, supple

Resp: Mild wheezes b/l, no rales, rhonchi, not in respiratory distress

CV: Tachycardic, regular rhythm, no murmurs, rubs, gallops

Abd: Tender to palpation especially in the LUQ with voluntary guarding, no rebound or rigidity, Normal bowel sounds

GU: CVA tenderness to percussion over left flank. Normal external genitalia.

Ext: Well-perfused

Skin: Diaphoretic, no lesions or rashes

Neuro: CNII-XII intact. Strength 5/5 upper and lower extremities b/l. SILT x 4. AOx3.

Labwork showed:

Lactate: 0.7

Albumin 2.9, tBili: 1.2, dBili: 0.4, Alk Phos: 63, ALT: 58, AST: 62

PT/INR: 13.9/1.2

Trop: 0.054

WBC: 6.3, HGB: 8.3, HCT: 23.9, MCV 86.7, RDW 13.9, PLT 75

Glu: 120, BUN 17, Cr 0.55, Na 132, K 3.9, CL 102, HCO3 23

Calcium 8.3, Mg 1.4

Urinalysis: WNL

 His EKG is below:

A chest x-ray was performed:

As well as a CT scan:

 And then, a test was ordered that confirmed the diagnosis. What was that test and the ultimate diagnosis?

TEST AND DIAGNOSIS

A parasite smear, which showed babesiosis that had resulted in atraumatic splenic rupture, causing the patient’s abdominal pain.

DISCUSSION

Background

Babesiosis is a protozoal intraerythrocytic infection. Many species of babesia lead to human infection globally, however B.microti causes the majority of infections in the United States. Collectively, babesia parasites are referred to as ‘piroplasms,’ deriving from the Latin word for pear, as babesia are often observed to resemble pear-shapes within infected red blood cells. Babesia is named after Victor Babes who discovered a protozoa causing hemolytic anemia in Romanian cattle. The first cases in the United States were described in Nantucket, Massachusetts in 1969 leading to the name “Nantucket Fever.”

The primary vector responsible for the majority of disease transmission is the Deer Tick, Ixodes scapularis. However, cases have been transmitted via organ transplantation, blood transfusion, and vertically from mother to fetus. The onset of clinical features of disease is typically from 1 to 4 weeks following tick bite. Interestingly, clinical symptoms may take up to 6 months to manifest in cases contracted via blood transfusion. The majority (75%) of cases are diagnosed between the months of June to August. The distribution of babesiosis cases across the United States mirrors that of the I.scapularis, which has substantially expanded its geographic distribution in recent decades due to a variety of human and environmental factors, as seen below: 

There is an intricate connection between babesia, mouse, and tick life cycles as they relate to the propagation and transmission of disease. A simplified babesia life cycle is represented below:

• A deer tick takes a blood meal from a white-footed mouse, introducing babesia sporozoites into the mouse.

• Sporozoites infect mouse red blood cells and become take on a ring form, becoming trophozoites.

• Trophozoites bud asexually into a tetrad of merozoites (Maltese cross).

• Merozoites lyse the red blood cells and become gametocytes.

• Gametocytes are ingested by another tick where they reproduce sexually in the tick gut.

• Sporozoites are re-formed in the tick salivary gland.

• Ticks introduce sporozoites into humans during blood meals, where a similar intraerythrocytic process occurs, however, humans are dead-end hosts whereby additional tick meals off an infected human do not result in reuptake of gametocytes.

Clinical manifestations of babesiosis can be thought of in two flavors, mild-to-moderate and severe. In mild-to-moderate disease, parasitemia is typically less than 4% and clinical symptoms are often vague and non-specific. Patients commonly present with fever, myalgia, chills, and fatigue. Less frequently, patients present with abdominal pain, sore throat, arthralgia, diarrhea, and headache. Lab findings often demonstrate hemolytic anemia, and thrombocytopenia. Transaminitis and azotemia is less commonly seen. White blood cell count is variable. Rash is seldom present and, when present, should raise suspicion for concurrent Lyme infection. Severe disease is often associated with parasitemia greater than 4%. Complications associated with higher parasite burden include acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation, altered mental status, shock, congestive heart failure, splenic infarcts, or as was the case in our patient, atraumatic splenic rupture. Of these severe complications, ARDS is most common. Interestingly, while atraumatic splenic rupture is an associated complication of babesiosis, the majority of cases have low parasite burden (<4%) and are not associated with additional severe manifestations of disease. Patients greater than 50 years of age, neonates, immunocompromised, and asplenic patients are at greatest risk for developing severe disease.

The mortality of babesiosis is between 3 and 9 percent among hospitalized patients. In patients contracting babesiosis through blood transfusion, mortality approaches 20 percent. Mortality in patients with babesiosis who develop ARDS approaches 40 percent. While the majority of treated cases fully resolve, there are reports of clinical relapse despite adequate treatment. In general, relapsed cases are usually less severe, return typically within days to weeks of treatment completion, and are most commonly seen in immunocompromised or asplenic patients.

Diagnosis

The diagnosis of babesia is made through the use of several testing modalities. Blood parasite smear is the primary method of detection. Peripheral blood smear can help identify intraerythrocytic parasites at different lifecycle stages. The presence of the merozoite in tetrad formation is pathognomonic for babesiosis, and is referred to as the Maltese Cross (C below and black arrow). On peripheral smear, the presence of extracellular trophozoite forms (D) is associated with very high parasitemia and typically more severe clinical manifestations of disease.

If a clinician has a high suspicion for infection and the initial smear is negative, a repeat smear may be performed with the addition of polymerase chain reaction (PCR). PCR is more sensitive than peripheral smear and is useful when parasite load is very low. In addition, PCR can also distinguish between babesia species, though is less likely to be clinically relevant in the United States. Serologic testing is available for babeisa, though it is unlikely to be clinically useful as the onset of disease can precede the presence of a positive immunoglobulin titer, and a positive titer may reflect merely a prior infection. Given the shared vector of disease transmission, it is essential for clinicians to consider appropriate co-infection. Up to two-thirds of patients diagnosed with Babesiosis will also have Lyme. One-third of patients will also have anaplasmosis. 

Treatment

Patients with mild-to-moderate parasitemia (<4%) may be treated with atovaquone and azithromycin, whereas severe parasitemia (>4%) should be treated with clindamycin and quinine. Alternative treatment options include doxycycline and proguanil. Treatment duration is 10 days for immunocompetent hosts, and either a total of six weeks or two weeks beyond the last positive peripheral smear in immunocompromised patients.

CASE RESOLUTION

The patient went to the operating room for splenectomy and was treated with a course of atovaquone and azithromycin. He made a full recovery and was discharged home.

Author: Samuel Goldman MD, MPH

Faculty Reviewer: Alison Hayward, MD

REFERENCES

1. Weiss LM, Wittner M, Tanowitz HB. The treatment of babesiosis. N Engl J Med. 2001;344:773

2. American Society for Microbiology - Microbe Library, ASMMicrolibrary.org. Accessed 8-16-2020.

3. Vannier E, Krause PJ. Human babesiosis. N Engl J Med. 2012;366:2397–407.

4. CDC.gov DPDx - Laboratory Identification of Parasites of Public Health Concern. Accessed online 08-16-2020. 

5. Prevention, CDC - Centers for Disease Control and. "CDC2 - Babesiosis" www.cdc.gov. Retrieved 08-16-2020.

6. Diuk-Wasser, M.A, Gatewood, A.G., Cortinas, M.R., Yaremych-Hamer, S.; Tsao, J., Kitron, U., Hickling, G.; Brownstein, J.S.; Walker, E., Piesman, J., Fish D. 2006. Spatiotemporal Patterns of Host-Seeking Ixodes scapularis Nymphs (Acari: Ixodidae) in the United States. Journal of Medical Entomology. 42(2): 166-176.

7. Homer, Mary J. et al. Babesiosis. Clinical Microbiological Reviews. 13: 451-469, No. 3. July, 2000.