A very wealthy family from the Boston area has been looking forward to their vacation on Nantucket Island for several months. (Housing on this exclusive resort island is usually reserved years in advance, so they were lucky to find a place on relatively short notice.) The family especially enjoys hiking through the undeveloped parts of the island that have been preserved in their more or less natural state because this provides such a sharp contrast to their everyday experiences in downtown Boston. Occasionally, they manage to spot birds and other forms of wildlife that are now rare in the city. However, being from the big city, they are unaware that the lovely, undeveloped parts of this island also provide a fine environment for ticks and other such creatures, so they fail to use insect repellent or other precautions against bites.

About a week into the vacation, while the family is on one of their beloved pastoral jaunts through the wilderness, their 16-year-old son notices a biting sensation on his leg. Assuming that it's just a mosquito, he ignores it. About two weeks after returning from their vacation, the son begins to experience malaise. Over the next two weeks, he develops a combination of irregular fever, headache, chills, sweating, myalgias, fatigue, and pronounced weakness. These symptoms persist for over two weeks, without any signs of letting up, so the family seeks medical advice. The boy's vital signs are: T = 38.5ºC, R = 18, P = 85, BP = 105/75 mm Hg. The physical examination detects mild hepatomegaly and splenomegaly, but there are no other remarkable findings. The physician asks the family about various recent activities, including travel, meals eaten at restaurants, etc. They mention the vacation on Nantucket Island but point out that it has been several weeks since they returned, so they don't see how that could be related to their son's problem.

Question 2.1: What is your preliminary diagnosis?

The fact that the family spent time hiking in an area where ticks are endemic should be considered suspicious, even if the patient fails to recall being bitten. Lyme disease has been a significant problem in this part of the country, but the symptoms are not characteristic of this disease. Some arthropod-borne diseases, such as malaria, might cause symptoms like this, but can most likely be eliminated because the family has not traveled outside of the U.S. One tick-borne disease that is endemic to the northeast U.S. coast (albeit not terribly common in humans) is babesiosis, which should be considered in febrile patients who have traveled in an endemic area.

Question 2.2: What is the differential?

The differential includes amebiasis, ehrlichiosis, hepatic abscess, leptospirosis, malaria, salmonellosis (including typhoid fever), acute viral hepatitis, and hemorrhagic fevers. As previously noted, some of these probably can be eliminated based on the family's travel history.

Question 2.3: What tests should you perform?

If babesiosis is suspected, you should order a CBC with differential, serum chemistry, and urinalysis. You should also do Giemsa- or Wright-stained thick and thin blood films, which can be examined for the presence of intraerythrocytic parasites.

Test Results

The CBC indicates WBC count of 3680/microliter, Hgb 11.7g/dL, Hct 35.1%, MCB 89 fL, and platelet count of 144,000/microliter. Serum chemistries indicate total protein 5.7 g/dL, albumin 3.7 g/dL, alkaline phosphatase 192 U/L, total bilirubin 3.3 mg/dL, direct bilirubin 0.8 mg/dL, LDH 1050 U/L, AST 101 U/L, and ALT 40 U/L. The urinalysis shows pH 6.5, sp gr 1.016, no glucose, 2+ protein, 2+ blood, no ketones, leukocyte esterase negative, and nitrite negative. Urine microscopic examination shows no RBCs or WBCs.

Microscopic examination of Giemsa-stained blood films indicates the presence of Babesia ring forms and tetrads in some of the erythrocytes.

Question 2.4: What is the most likely causative agent?

The causative agent is the protozoan Babesia. More than 70 species are found in Europe, Africa, Asia, and North America. Babesia microti is responsible for virtually all babesiosis cases occurring along the northeastern seaboard of the U.S. Infection can be confirmed serologically, using an indirect immunofluorescent assay (IFA) that is specific for B. microti.

Question 2.5: How does this agent produce the illness?

B. microti trophozoites that enter the bloodstream infect erythocytes and multiply (via binary fission) therein. This process results in lysis of the erythrocytes and release of the merozoite form of the protozoan. The merozoites also infect and replicate in erythrocytes and this maintains the infection. The symptoms of the disease result primarily from the continued destruction of leukocytes.

Question 2.6: How is this disease transmitted?

Babesiosis is most often transmitted by the tick Ixodes dammini, which acts as a vector. Natural reservoir hosts in the northeastern U.S. include field mice, voles, and other small rodents. Blood transfusions are another source of babesiosis. More than 20 transfusion-related cases have been reported to date. Parasites usually were not detected in the donors, but serologic testing of their blood for Babesia yielded positive results.

Question 2.7: How is this disease treated?

B. microti infections in patients with intact spleens are usually self-limiting without treatment, although symptoms may persist for months, with or without treatment. Because silent parasitemia may have prolonged symptoms and signs, treatment is advised for all patients. Treatment with a combination of quinine sulfate (650 mg of salt orally tid) plus clindamycin (600 mg orally tid or 1.2 g parenterally bid) for 7 to 10 days is often effective but might not always eliminate the parasites. Especially severe infections, with high-level B. microti parasitemia in asplenic individuals, have been successfully treated using exchange transfusions in addition to quinine and clindamycin therapy.