Babesia Species (Babesiosis)

Description of The Pathogen

Babesia spp. belong to the phylum Apicomplexa along with Cryptosporidium, Plasmodium, and Toxoplasma . Babesia organisms require both a tick vector and a vertebrate host to complete their complex life cycle. The parasites directly infect erythrocytes (without the pre-erythrocytic–hepatic stage that some plasmodia exhibit), where trophozoites divide by sporogony (budding) into two or four merozoites, depending on the species. ^{, ,} Egress of the merozoites occurs with lysis of the erythrocyte, leading to invasion of other red blood cells and clinical symptoms. ^, A detailed description of the life cycle is available ( http://www.cdc.gov/parasites/babesiosis/biology.html ).

Most Babesia sp. are transmitted by Ixodes ticks and have a primary vertebrate reservoir, whereas humans are accidental hosts ( Table 258.1 ). Nymphal ticks are the primary vector because of their small size and summer feeding activity, but transmission of B. microti requires 36–72 hours of tick attachment. The tick vector for B. microti in the eastern US is Ixodes scapularis, and the primary reservoir is the white-footed mouse. ^{, ,} Adult ticks feed on white-tailed deer, ensuring their survival and amplifying the tick population, but the deer are not a reservoir for B. microti . Because I. scapularis also transmits Anaplasma phagocytophilum, Borrelia burgdorferi, Borrelia miyamotoi, Borrelia myonii, Ehrlichia muris eauclairensis, and Powassan virus , coinfections occur. ^, Transmission also occurs without the tick vector in congenital and perinatal cases, . during transfusion of blood from parasitemic donors, and following organ transplantation. ^,

Epidemiology

Initially described as the cause of febrile hemoglobinuria in cattle in 1888, Babesia are responsible for significant disease burden in livestock and animals. ^, The first human case was reported in a splenectomized male in 1957 in Europe, and the first case in a healthy individual was reported in 1970 from Nantucket Island, Massachusetts (called Nantucket fever ). In the 1970s and 1980s, B. microti was found to be endemic in Massachusetts (Nantucket Island, Martha’s Vineyard, Elizabeth Islands, and Cape Cod), Rhode Island (Block Island), southeastern Connecticut, and New York (Shelter Island, Fire Island, and eastern Long Island). During the same period, B. divergens caused sporadic but more severe disease in asplenic adults in Europe. ^, During the past five decades the incidence of babesiosis in the US has increased substantially, ^{, , ,} and with the recent use of molecular studies, newly recognized species continue to emerge in ever-expanding geographic areas. ^{, , ,}

National surveillance for human babesiosis in the US started in 2011, with required reporting in 18 states and New York City, which expanded to 40 states reporting in 2018. ^, The national annual average case count has doubled since 2011 due to increasing incidence and geographic spread. ^, A total of 2358 confirmed and probable cases of babesiosis were reported in 2017, and 2161 cases were reported by 28 of the 40 states in 2018. About 3% of cases occur in children ≤19 years of age. There appears to be underreporting in areas of emerging babesiosis, likely owing to lack of specific clinical signs (such as erythema migrans rash in Lyme disease) and low index of suspicion among medical providers. Babesiosis primarily is seasonal, with >70% of cases having symptom onset between June and August, when nymphal ticks are most actively feeding, ^{, ,} but only 45% of patients recall a tick bite in the 8 weeks before symptom onset. The median age of reported US cases is 63 years, and 65% are males.

Currently, B. microti infection is endemic in the northeastern ^{, ,} and upper midwestern (Wisconsin and Minnesota ) US, with about 90% of cases consistently reported from 7 states (Connecticut, Massachusetts, Minnesota, New Jersey, New York, Rhode Island, and Wisconsin) where transmission is well established. ^, Since 2016, Maine is regularly reporting more cases than either Wisconsin or Minnesota. Community-based serosurveys in endemic areas of the northeastern US performed in the late 1970s–1990s revealed antibodies to B. microti in 2%–10% of residents, ^{, , ,} whereas testing of blood-donor specimens from 2000–2012 in these same areas found antibodies in 1%–1.4% of samples. ^,

The spread of B . microti continues, with increased numbers of cases within endemic areas ^{, , ,} and the appearance of cases in contiguous areas such as Pennsylvania and Canada ^, ( Fig. 258.1 ). Coinfection of mice with Borrelia burgdorferi increases transmission of B. microti to I. scapularis ticks and likely increases the emergence of babesiosis in Lyme endemic areas. In New York state, 29% of patients serologically confirmed to have Lyme disease were also seropositive for B. microti , and 7.7% of 52 adults with erythema migrans had active coinfection with B. microti based on the smear or PCR results. Although B . microti is the most common species in the US, rarely, B. duncani and B. duncani −type infections have been reported in Washington and California. ^{, ,} B. divergens −like infections have occurred in Missouri, Kentucky, Washington State, Michigan, and Arkansas.

In Europe, human babesiosis is much less common than in the US, with reported cases totaling <100. Most cases result from B. divergens infection in asplenic individuals, ^{, , ,} although cases in healthy persons have been reported. Babesiosis has been reported in eastern and western Europe, including in the UK, Ireland, and Scandinavia. A few cases of B. venatorum infection have been described. ^, Indigenous B. microti in Europe was first reported in Switzerland and Germany, but the disease likely is underrecognized and underreported owing to its less fulminant course and lack of cross-reactivity with serologic tests for B. divergens . ^, In Asia, cases of B. microti , B. venatorum, a B. crassa -like pathogen, and novel strains (KO1, XXB/HangZhou) have been reported. ^{, ,} Human babesiosis also has been reported in Africa, Australia, and South America. ^, A further increase in the number of cases is expected with growing number of immunocompromised people and with the increase in tick vector populations linked to expanding deer populations ^{, , ,} and climate change.

Clinical Manifestations

Clinical manifestations of babesiosis occur on a spectrum from asymptomatic infection to severe disease that can be fatal. The incubation period following a tick bite usually is 1–4 weeks (as long as 6 weeks), and 1–9 weeks (as long as 6 months) following transfusion. ^{, ,} Between 32% and 62% of infections are asymptomatic. ^{, , ,} Infections can become symptomatic after many months of asymptomatic parasitemia.

Clinical infection most often is a nonspecific influenza-like illness, when the diagnosis is rarely made. ^, A gradual onset of malaise and fatigue is followed by fever as high as 40.5°C (105°F). The most common symptoms of B. microti infection are summarized in Table 258.2 . Additional symptoms reported in two series totaling 84 patients included emotional lability in 50%, neck stiffness in 48%, sore throat in 31%, vomiting in 20%, joint swelling in 11%, and conjunctivitis in 11%. ^, Individuals noted an average of 9 separate symptoms lasting 10 weeks. Persistent parasitemia, as detected by PCR, can last for several months to >1 year, even with treatment.

Physical findings often are limited to fever in mild cases, although jaundice, pallor, mild hepatosplenomegaly, dark urine, and occasionally pharyngeal erythema can be present. ^{, ,} Noncardiac pulmonary edema and ocular manifestations, such as retinal splinter hemorrhages, have been described.

Typically, B. divergens and B. divergens −like infection is more fulminant, ^{, ,} resulting in a case fatality rate of 42%. However, B. microti also can cause severe disease, especially in those with risk factors, but overall mortality is <1%. Risk factors for severe babesiosis, in addition to infection with B. divergens, include age >50 years, male sex, asplenia, immunecompromising conditions (including AIDS), immunosuppressive therapy, and malignancy. In those with AIDS, babesiosis can manifest as fever of unknown origin as well as persistent or relapsing disease. An underlying immunodeficiency should be considered in any patient with severe or prolonged babesiosis. Coinfection with Borrelia or Anaplasma spp., or both, appears to cause more severe disease ^{, , ,} ; therefore any patient with prolonged or severe symptoms also should be tested for these pathogens. About 45% of reported US patients with babesiosis have required hospitalization, ^, and most have a comorbidity (or comorbidities), such as asplenia, heart disease, hypertension, chronic obstruction pulmonary disease, alcoholism, and diabetes. Children aged 0–19 years have significantly fewer symptoms (40% being symptom free), have significantly shorter duration of illness, and are hospitalized infrequently, particularly compared with people >50 years. Patients with anemia (hemoglobin concentration <10 g/dL) or high parasitemia (>10%) are more likely to have complications. Reported complications include acute respiratory distress syndrome, disseminated intravascular coagulopathy, congestive heart failure, acute renal failure, myocardial infarction, splenic infarction, splenic rupture, ^, warm autoimmune hemolytic anemia in asplenic patients, septic shock, and death. ^,