B
abesiosis is a zoonotic infection caused by the
BACKGROUND: Babesiosis is a potentially life-
tickborne intraerythrocytic protozoan parasite
threatening zoonotic infection most frequently caused by
Babesia.1 In the United States, human babesiosis
the intraerythrocytic parasite Babesia microti. The
is attributed primarily to infection with
pathogen is usually tickborne, but may also be
transfusion or vertically transmitted. Healthy persons,
B. microti, which is endemic to portions of the Northeast
including blood donors, may be asymptomatic and and upper Midwest.2-5 Seven states have historically been
unaware they are infected. Immunocompromised considered endemic: Connecticut, Rhode Island, New
patients are at increased risk for symptomatic disease. York, Massachusetts, New Jersey, Minnesota, and Wiscon-
STUDY DESIGN AND METHODS: All reported sin. In addition, we consider Maine and New Hampshire
community-acquired babesiosis cases in New York from endemic based on recent published literature and Penn-
2004 to 2015 were evaluated, enumerated, and sylvania has seen increasing incidence and some endemic
characterized. All potential transfusion-transmitted foci.6-10 Distribution is variable; endemic states have
babesiosis (TTB) cases reported through one or more of hyperendemic foci and areas at much lower risk. Babesio-
three public health surveillance systems were sis can also be caused by other Babesia species, such as
investigated to determine the likelihood of transfusion B. duncani on the West Coast of the United States.11-14
transmission. In addition, host-seeking ticks were actively B. microti is usually transmitted to humans, as an
collected in public parks and other likely sites of human incidental host, by the black-legged tick, Ixodes scapularis.
exposure to B. microti. The organism is maintained naturally through an enzootic
RESULTS: From 2004 to 2015, a total of 3799 cases of reservoir, primarily the white-footed mouse (Peromyscus
babesiosis were found; 55 (1.4%) of these were linked to leucopus), while deer can nourish and transport adult ticks
transfusion. The incidence of both community-acquired to expanding geographic areas.15,16 Tick larvae acquire the
babesiosis and TTB increased significantly during the 12-
year study period. The geographic range of both ticks ABBREVIATIONS: ERI(s) 5 entomologic risk index(-es);
and tickborne infections also expanded. Among TTB IFA 5 indirect fluorescent antibody; TTB 5 transfusion-
cases, 95% of recipients had at least one risk factor for transmitted babesiosis.
symptomatic disease. Implicated donors resided in five
From the 1Wadsworth Center and the 2Bureau of
states, including in 10 New York counties. More than half
Communicable Disease Control, New York State Department of
of implicated donors resided in counties known to be
Health, Albany, New York; 3Biomedical Services, Scientific
B. microti endemic.
Affairs, American Red Cross, Rockville and Gaithersburg,
CONCLUSION: The increasing incidence of TTB
Maryland; and 4New York Blood Center, New York, New York.
correlated with increases in community-acquired
Address reprint requests to: Susan L. Stramer, Scientific
babesiosis and infection of ticks with B. microti.
Support Office, American Red Cross, 9315 Gaither Road, Gai-
Surveillance of ticks and community-acquired cases may
thersburg, MD 20877; e-mail: Susan.Stramer@redcross.org.
aid identification of emerging areas at risk for Babesia
This study was funded in part by US National Institutes of
transfusion transmission.
Health, Grant AI097137.
Received for publication September 12, 2017; revision
received November 3, 2017; and accepted November 11, 2017.
doi:10.1111/trf.14476
C 2018 AABB
V
TRANSFUSION 2018;;660–668
organism via a blood meal from an infected rodent host MATERIALS AND METHODS
and continue to carry the parasite as they develop into
Case finding
nymphs (approximately the size of a poppy seed), the
stage most likely to transmit the organism to humans. In This is a retrospective study of reported community-
addition to tickborne transmission, B. microti may be acquired babesiosis and TTB cases that occurred in New
transmitted by blood transfusion from asymptomatic York from 2004 to 2015. For TTB cases, the date of expo-
blood donors.17 Vertical transmission has also been sure was based on the date of implicated transfusion. The
reported rarely.18 The parasite invades red blood cells primary data source was public health records. Physicians
(RBCs), resulting in an infection that can range from are required to report babesiosis cases to the local health
asymptomatic to severe disease. Symptomatic disease department of the patient’s county of residence. The pub-
presents most commonly with fever, chills, malaise, myal- lic health surveillance investigation process includes two
gia, gastrointestinal symptoms, and/or hemolytic ane- questions regarding possible transfusion or transplanta-
mia.19 Fulminant disease can manifest with disseminated tion within the previous 6 months. Cases with an affirma-
intravascular coagulation, hemodynamic instability, and tive response to either question are referred to the blood
potentially fatal multiorgan dysfunction.19 and tissue oversight program for investigation. Also, labo-
The first case of human babesiosis in New York was ratories must report positive Babesia-related test results to
identified in 1975, and the disease was designated a the State Department of Health using an electronic report-
reportable communicable disease by the New York State ing system. In addition, babesiosis cases that may be
Department of Health in 1986.20 Shelter Island and the
transfusion transmitted are reportable directly to the
South Fork of Long Island, east of the Shinnecock Canal,
blood and tissue oversight program. Case investigation
have been and continue to be hyperendemic foci. How-
included assessing time frames and recipient medical cir-
ever, cases have been reported in larger numbers and in
cumstances, donor laboratory testing, and follow-up
expanding geographic areas. Outside New York, other
interviews. If a blood component and donor were impli-
high-incidence areas include coastal regions of southern
cated, efforts were made to identify recipients of cocom-
New England, especially all coastal regions of Connecti-
cut, Martha’s Vineyard and Nantucket Island in Massachu- ponents from the implicated donation and previous
setts, and Block Island in Rhode Island. Babesiosis recipients of blood components from the implicated
became nationally notifiable in 2011, meaning that, in donor.
states in which babesiosis is a reportable communicable
disease (31 as of 2014), the state health department is Case criteria and classification
expected to report confirmed cases to the Centers for Dis- We used the following case criteria to determine Babesia
ease Control and Prevention in a nonidentifying fashion, infection in patients: diagnosed Babesia infection con-
for surveillance purposes, using a standardized case defi- firmed by laboratory testing. Parasitologic evidence
nition.21 To be classified as confirmed, a case of babesiosis included observation of Babesia organisms on peripheral
requires symptoms and supportive laboratory findings. blood smear or detection of Babesia DNA by a molecular
However, a blood donor may be considered implicated method. Serologic evidence included positive results
even if confirmed case criteria are not met. (titer 256) by indirect fluorescent antibody (IFA) or
The incidence of transfusion-transmitted babesiosis immunoglobin G (IgG) immunoblot. Additional criteria
(TTB) in the United States is increasing. A 2011 report
for TTB were: 1) receipt of a blood component within a
identified 159 cases of TTB attributed to B. microti from
plausible time frame and 2) absence of evidence that
1979 to 2009, with the majority of them (77%) occurring
another route was more likely than transfusion. A TTB
between 2000 and 2009.17 TTB cases have been linked to
case was considered definite if an extant segment dem-
RBCs, frozen deglycerolized RBCs, and whole blood–
onstrated evidence of infection. A TTB case was consid-
derived platelet (PLT) concentrates (presumably from
ered probable if linked, in a plausible time frame, to a
residual RBCs).17,22 There have been no confirmed reports
of cases associated with fresh-frozen plasma, plasma fro- donor found positive by nucleic acid testing or a titer of
zen within 24 hours, apheresis PLTs, or cryoprecipitate. 64 or more on serologic testing on a specimen collected
B. microti is currently the most common RBC transfusion- subsequently. A TTB case was considered possible if no
transmitted pathogen reported to the US Food and Drug donor was implicated, but it was not possible to test all
Administration through the Biological Product Deviations donors, and the patient had no other plausible risk. If all
Reporting system, accounting for 20 of 26 (77%) reports of associated donors were seronegative or the patient’s
pathogen transmission in Fiscal Year 2015.23 Babesia was infection predated any transfusion(s), the case was
linked to three of five reports of fatalities in the United excluded as transfusion transmitted. Cases not linked to
States attributed to RBCs contaminated with an infectious transfusion or transplantation were considered commu-
agent in Fiscal Year 2011 to 2015.24 nity acquired.
Fig. 1. Number of community-acquired and TTB cases, 2004 to 2015. [Color figure can be viewed at wileyonlinelibrary.com]
Fig. 2. Incidence rate (per 100,000 population) of human babesiosis, prevalence of B. microti in host-seeking I. scapularis
nymphs, and ERI in New York State, 2008 to 2015. [Color figure can be viewed at wileyonlinelibrary.com]
symptoms was 35.9 days (median, 34 days; range, 8- and 31% of all patients less than 5 years of age. While
91 days). The mean maximum parasitemia, when known, there was an even distribution of TTB cases across the
in TTB cases was 6.1% (median, 5%; range, 0.01%-29%). sexes (49% male, 51% female), the distribution of all
For both all cases and TTB cases, the patient age and reported babesiosis cases was more heavily skewed
sex distributions are shown in Table 1. TTB cases toward males (62% male, 38% female). Although the dif-
accounted for 9.2% of cases among children up to age 19, ference was not significant (v2 5 3.8213, p 5 0.0506), it is
meaningful in that it highlights the difference between the the 12 years studied (data not shown). A large proportion
sex distribution of TTB versus all cases. The implicated (27/55, 49%) of implicated donations took place in July,
donors in the TTB cases were more likely to be male (84% August, or September, consistent with exposure occurring
male, 16% female), compared to the overall donor popula- during the known peak nymphal I. scapularis tick activity
tion, which is more evenly split between the sexes (57% from mid-May through mid-August.6 In contrast, little
male, 43% female). Comparison of the sex distribution of activity was seen in March and April, providing only two
the three groups specific to this study, TTB cases, (4%) of the total implicated donations over the 12-year
community-acquired babesiosis cases, and implicated study interval. However, it is important to note that at
donors, showed a significant difference (v2 5 14.77, least one implicated donation took place in each month
p 5 0.0006). of the year.
Figure 3 shows all implicated donations for years Entomologic risk index is a measure of tickborne dis-
2004 to 2015 stratified by month of donation. Month of ease risk: the product of tick abundance and pathogen
implicated donation was relatively evenly distributed over prevalence in host-seeking ticks from a given location.
Babesiosis incidence rates per 100,000 population and
B. microti ERI, by New York county, for years 2004, 2008,
TABLE 1. Age and sex distribution of TTB and 2012, and 2015 are shown in Fig. 4. The increase in inci-
community-acquired babesiosis cases and sex dence across the counties in the Downstate and Lower- to
distribution of implicated donors*
Mid-Hudson Valley regions can be seen in the time pro-
All babesiosis
Age (years) cases TTB cases % TTB cases gression displayed, with a corresponding increase in
<1 7 (0.2) 2 (3.6) 28.6 B. microti ERI. Three counties—Columbia, Dutchess, and
1-4 6 (0.2) 2 (3.6) 33.3 Suffolk—saw significant increases in incidence over the
5-19 85 (2.2) 5 (9.1) 5.9 12-year study period (Fig. 5): Columbia County’s inci-
20-29 99 (2.6) 3 (5.5) 3.0
30-39 238 (6.3) 4 (7.3) 1.7 dence increased from 0.0 to 37 cases per 100,000 popula-
40-49 488 (12.8) 9 (16.4) 1.8 tion from 2004 to 2015 (R2 5 0.6634, p 5 0.0013);
50-59 809 (21.3) 4 (7.3) 0.5 Dutchess County’s incidence increased from 2.4 to 25.3
601 2063 (54.3) 26 (47.3) 1.3
Unknown 4 (0.1) 0 (0.0) 0.0 cases per 100,000 population (R2 5 0.4385, p 5 0.0190);
Suffolk County’s incidence increased from 4.0 to 14.2
Sex All babesiosis cases TTB cases Implicated donors
cases per 100,000 population (R2 5 0.7980, p < 0.0001);
Male 2355 (62.0) 27 (49.1) 46 (83.6)
Female 1444 (38.0) 28 (50.9) 9 (16.4) and Westchester County’s incidence increased from 1.0
Total 3799 55 55 to 5.8 cases per 100,000 population during this
* Data are reported as number (%). period, although this increase was not statistically signifi-
cant. New York State also saw a significant increase from
Fig. 3. Distribution of TTB cases by month of implicated donation, 2004 to 2015. [Color figure can be viewed at wileyonlineli-
brary.com]
Fig. 4. County-level incidence rates (per 100,000 population) of human babesiosis (left) and B. microti ERIs (right), 2004, 2008,
2012, and 2015.
0.5 to 3.0 cases per 100,000 population from 2004 to 2015 prevalence rates of B. microti in host-seeking nymphs and
(R2 5 0.8136, p < 0.0001). During the study period, there human babesiosis incidence (r 5 0.57, p < 0.0001), and 3)
was a positive association between 1) nymphal tick density B. microti ERI and human babesiosis incidence (r 5 0.58,
and human babesiosis incidence (r 5 0.58, p < 0.0001), 2) p < 0.0001; Table 2).
Fig. 5. Babesiosis incidence rates (per 100,000 population) in New York State and four highest incidence counties, 2004 to 2015.
[Color figure can be viewed at wileyonlinelibrary.com]
TABLE 2. Association between B. microti ERI and human babesiosis incidence rates in New York State,
2008 to 2015
Number Mean nymph Mean babesiosis Spearman
Year of counties density (ticks/m) Mean ERI* incidence correlation p value
2008 18 0.466 0.009 2.283 0.681 0.0019
2009 23 0.428 0.003 1.530 0.502 0.0146
2010 21 0.207 0.002 1.681 0.472 0.0308
2011 20 0.424 0.005 2.590 0.572 0.0084
2012 24 0.191 0.005 1.625 0.699 0.0001
2013 32 0.426 0.020 4.281 0.776 <0.0001
2014 54 0.135 0.004 2.367 0.612 <0.0001
2015 50 0.189 0.004 3.532 0.681 <0.0001
* ERI is the product of B. microti prevalence in host-seeking ticks and tick abundance.
All implicated donors resided in the northeastern undergone splenectomy, 11 (65%) had a hemoglobinopa-
region of the United States, with a majority (55%) residing thy (b-thalassemia or sickle cell disease). In addition, two
within one of the four known highest-incidence counties spleen-intact patients had sickle cell disease, in which
(of 62) in New York (Suffolk, Westchester, Dutchess, and functional hyposplenism is common.27 Other identified
Columbia Counties). In addition, one upstate donor had risk factors included treatment for a malignancy or other
traveled to Connecticut, seven implicated units were col- immunosuppression (11, 20%), and history of hematopoi-
lected in New Jersey, and blood units imported from out- etic progenitor cell or solid organ transplant (two and
of-state blood centers had been collected in Massachu- three patients, respectively). One patient (2%) had three
setts (3), Rhode Island (1), or Pennsylvania (1). risk factors, eight (15%) had two risk factors, and 44 (80%)
All except two (5%) of the reported TTB patients had had one risk factor. The two cases (4%) not linked to a rec-
at least one established risk factor for symptomatic babe- ognized risk factor included a 58-year-old with liver dis-
siosis among their age or underlying comorbidity(-ies). ease and a 50-year-old with iron deficiency anemia. Two
Although more than half (28/55, 51%) of affected recipi- patients (4%) died of Babesia infection in the context of
ents were either 60 years of age or older (26, 48%) or less their underlying comorbidities: a woman in her 90s with
than 1 year of age (two, 4%), the most notable risk factor gastrointestinal bleeding and a man in his 60s status post–
was asplenia (17/55, 32%). Of the 17 patients who had hip surgery complicated by infection.
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