SELF ASSESSMENT ANSWERS Unusual cause of fever, jaundice, and hepatomegaly in a middle aged man

Q1: In this patient’s clinical context, how do you interpret the laboratory tests on admission (table 1; see p 566) and those done between days 2–4 (table 2; see p 566)? This patient had a subacute febrile illness with constitutional symptoms and progressive jaundice. Initial laboratory tests showed severe anaemia with an increased reticulocyte count (corrected for the degree of anaemia) and red cell distribution width, predominantly direct hyperbilirubinaemia, modest elevations in transaminases and alkaline phosphatase, hypoalbuminaemia, and mild renal impairment. The abdominal computed tomogram finding of asplenia was later confirmed to be due to splenectomy done during trauma surgery many years earlier. This imaging study also excluded biliary obstruction, pyaemic liver abscess, and tumour as causes of his jaundice. Serial blood tests done between days 2–4 revealed decreasing haemoglobin levels, increasing macrocytosis and reticulocytosis, high lactate dehydrogenase, and low haptoglobin levels. This was consistent with haemolysis. The negative blood cultures and absence of radiographic evidence of biliary obstruction made cholangitis less likely as a cause for his fever. Infectious conditions that can produce haemolytic anaemia are listed in box 1. Q2. What does the blood smear show? What is the differential diagnosis? The peripheral blood smear shows an erythrocyte infected with Babesia microti (fig 1, arrow; see p 566) piroplasms, so called because they are pear shaped. The organisms within the red cell appear as darkly staining ring forms that are about 2 μm in size and contain pale blue cytoplasm (fig 1, inset; see p 566). These intraerythrocytic ring forms closely resemble Plasmodium falciparum. Three distinguishing features differentiate the two: babesiae form tetrads (“Maltese cross”), do not have haemozoin pigments within the affected red blood cells, and have extracellular merozoites. Geographic factors and travel history would also be relevant diagnostic pointers in deciding between the two agents. Babesiosis was first described in 1957 and is distributed worldwide, but most clinical cases have been described in the temperate regions of the United States and Europe. In North America, it is most endemic in the islands off the coast of Massachusetts, including Nantucket and Martha’s Vineyard and in eastern Long Island in New York. The predominant organism is Babesia microti, a natural parasite of rodents, which is transmitted by the bite of the tick Ixodes scapularis. Based on serosurveys, the estimated seroprevalence has been varyingly reported to be between 8% and 16%, but true prevalence is difficult to estimate since most human infections are subclinical. In asplenic and immunocompromised individuals, the disease is often more severe. More recently, in the western United States, a yet unnamed piroplasm (designated WA1) has been described as a putative agent for human babesiosis, mostly in asplenic individuals. The overall mortality rate for clinical cases of B microti is about 5% in the United States. In contrast, symptomatic babesiosis is much less prevalent in Europe, with fewer than 30 cases reported so far, mostly from the British Isles and France. Most such cases (83%) are due to Babesia divergens, a bovine pathogen. B divergens tends to produce a more severe illness with a shorter incubation period (1–3 weeks after the tick bite), tends to occur mostly in splenectomised individuals, and has a much higher mortality rate, about 42%. While seeing the piroplasms in stained preparations of thin blood smears remains the gold standard for diagnosis, immunofluorescence antibody test and polymerase chain reaction are also being used, mostly as epidemiological or research tools. Transfusion associated babesiosis has been described, as also has been coinfection with other tick-borne pathogens such as Borrelia burgdorferi (Lyme disease), ehrlichiae, and Bartonella bacilliformis (Oroya fever). Also, babesiosis tends to run a severe course in patients with AIDS. 2