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. 2012 Sep 5;87(3):529–537. doi: 10.4269/ajtmh.2012.12-0060

Epidemiology of Ehrlichiosis and Anaplasmosis among American Indians in the United States, 2000–2007

Arianne M Folkema 1, Robert C Holman 1, F Scott Dahlgren 1, James E Cheek 1, Jennifer H McQuiston 1,*
PMCID: PMC3435360  PMID: 22826495

Abstract

Ehrlichiosis and anaplasmosis infections among American Indians (AIs) have never been specifically examined, despite high rates of other tick-borne rickettsial diseases among AIs. The epidemiology of ehrlichiosis and anaplasmosis among AIs was analyzed using the National Electronic Telecommunications System for Surveillance (NETSS), Case Report Forms (CRFs), and Indian Health Service (IHS) inpatient and outpatient visits. The 2000–2007 average annual ehrlichiosis and anaplasmosis incidence among AIs reported to NETSS was almost 4-fold lower (4.0/1,000,000) than that using IHS data (14.9). American Indian cases reported from CRFs had a higher proportion of hospitalization (44%) compared with IHS (10%). American Indian incidence of ehrlichiosis and anaplasmosis was higher and showed a different age and geographical distribution than other races. These results highlight the need to improve collaboration between the ehrlichiosis and anaplasmosis surveillance systems for AIs so as to develop interventions that target the unique epidemiology and mitigate the burden of disease among this high-risk population.

Introduction

Ehrlichiosis and anaplasmosis are closely related tick-borne diseases that can be fatal if left untreated.1–4 Infection is caused by intracellular bacteria belonging to the order Rickettsiales, which are typically spread to humans by bites of infected ticks.2,5,6 Human ehrlichiosis is caused by transmission of Ehrlichia chaffeensis, Ehrlichia ewingii, or a newly discovered Ehrlichia species closely related to Ehrlichia muris,7–10 whereas anaplasmosis is caused by infection with Anaplasma phagocytophilum.11,12 Previously, because of their clinical similarities, these agents were all classified within the same genus Ehrlichia and generally referred to as ehrlichioses, but taxonomic changes have reclassified anaplasmosis into its own genus Anaplasma because they are genetically distinct.1,5,13 However, because of the similar clinical presentations of ehrlichiosis and anaplasmosis,3 the serologic cross-reactivity between diseases accompanied by inappropriate testing,14 the substantial number of cases reported with unknown or unspecified status, and the lack of a specific diagnostic code differentiating the diseases,15 these two diseases have been combined into a single group for analysis of their epidemiology unless otherwise noted.

Earlier studies have shown that in the United States, ehrlichioses caused by E. chaffeensis and E. ewingii are found mainly in the south-central states,1,16–18 whereas anaplasmosis is found mainly in the Northeast and upper Midwest states.1,19,20 To date, infection due to E. muris-like Ehrlichia species has only been reported in Minnesota and Wisconsin.10 Clinical symptoms of these diseases are similar and include chills, fever, headache, muscle aches, nausea, diarrhea, and general malaise.1,4,21 A rash has been reported in up to a third of E. chaffeensis cases, however is not a hallmark of the other infections.1,21 Complications in more severe cases include meningoencephalitis, respiratory distress, renal failure, hemorrhages, seizures, and neurologic disorders.22–24

The epidemiology of other tick-borne diseases, including Rocky Mountain spotted fever (RMSF), has shown that American Indian (AI) people are at higher risk for tick-borne infections compared with other race groups, in part because of their geographic proximity to ticks.22,25–27 Despite geographic overlap in disease distribution, no studies have been done to specifically examine the risk of ehrlichiosis and anaplasmosis among AIs. This study uses data from the National Electronic Telecommunications System for Surveillance (NETSS), the national Tick-borne Rickettsial Disease Case Report Forms (CRFs), and the Indian Health Service (IHS) inpatient and outpatient visits to examine the national occurrence of human ehrlichiosis and anaplasmosis among the AI population during 2000–2007.

Methods

NETSS.

Human ehrlichiosis and anaplasmosis were made nationally notifiable diseases in 1998 and are reported to the Centers for Disease Control and Prevention (CDC) by individual state and territory health departments through NETSS.28 Ehrlichiosis and anaplasmosis cases reported to NETSS were considered to be cases in this study if they met either the confirmed or probable case definition of the Counsel of State and Territorial Epidemiologists (CSTE) for ehrlichiosis and anaplasmosis.29,30 These cases include reported cases from the following subgroups: E. chaffeensis infection (formerly Human Monocytic Ehrlichiosis), A. phagocytophilum infection (formerly Human Granulocytic Ehrlichiosis), and Undetermined, Unspecified, or Other Agent (UUOA) cases which include those for whom insufficient laboratory evidence was available to specify the causative agent or where the causative agent was one other than E. chaffeensis or A. phagocytophilum, i.e., E. ewingii. These subgroups were combined into a single category for most of the analysis (unless otherwise noted) to account for cases that did not have conclusive laboratory test results and to allow for comparison to the IHS data that did not have the same subgroup classifications available.

Incidence rates for ehrlichiosis and anaplasmosis were calculated using confirmed and probable cases reported through NETSS and the corresponding bridged-race census population for 2000–2007.31 Incidence is considered a valid measure for NETSS data because even though there is no way to link each reported case by a patient identifier, and there are some reports of repeated infection over time,32,33 it is known that antibodies exist for a long time and provide some measure of immunity.3 Only cases with known race were used for the analysis; although 35% of NETSS cases had missing race, the distribution of cases with and without reported race in regards to age, sex, and case status were similar. Incidence rates (per 1,000,000 persons) were calculated overall and by year, race group, age group, and sex. Rates were compared using Poisson regression to determine rate ratios (RRs) and 95% confidence intervals (CIs); RRs comparing race groups were adjusted by state to control for potential confounding of race by geography.34 Tests of trend by year were determined using Poisson regression analysis.34 Median age at illness onset was compared by race using the Wilcoxon rank-sum test.35 Statistical tests were considered significant at the 0.05 level.

States that did not consider the disease reportable for a given year were excluded from the denominator for the appropriate years. During 2000–2007, E. chaffeensis and A. phagocytophilum were not reportable through NETSS in the following states (years): Alaska (2000–2001, 2005–2007), Colorado (2000–2003, 2005, 2007), District of Columbia (2000, 2003–2005, 2007), Hawaii (2000, 2006–2007), Iowa (2005–2007), Idaho (2000–2001, 2005–2007), Illinois (2000), Louisiana (2000, 2001, 2003–2005), Maryland (2000–2001), Mississippi (2001, 2007), Montana (2000–2001, 2006–2007), North Dakota (2000–2005, 2007), New Mexico (2000–2001, 2007), Nevada (2000, 2005, 2007), Oregon (2000), Pennsylvania (2003–2004), Vermont (2000), and Washington (2006–2007). During 2000, the UUOA category was reportable through NETSS only in New York. From 2001 to 2007, the UUOA category was not reportable for the following states: Alaska (2001, 2005–2007), Colorado (2001–2003, 2005, 2007), District of Columbia (2003–2006, 2007), Hawaii (2006–2007), Iowa (2005–2007), Idaho (2001, 2005–2007), Louisiana (2003–2005), Maryland (2001), Mississippi (2001, 2007), Montana (2001, 2006–2007), North Dakota (2001–2005, 2007), Nebraska (2007), New Jersey (2005–2006), New Mexico (2001, 2007), Nevada (2005, 2007), Pennsylvania (2003–2004), and Washington (2006–2007).

Tick-borne Rickettsial Disease CRFs.

In addition to NETSS reporting, CDC collects more specific demographic and epidemiologic information on ehrlichiosis and anaplasmosis cases through the use of Tick-borne Rickettsial Disease CRFs by individual state and territory health departments.36 Although NETSS and CRFs contain substantial overlap, these data are used as separate surveillance systems for monitoring the occurrence of ehrlichiosis and anaplasmosis in the United States.25 The CRFs were used to compare numbers of cases and analyze clinical outcomes including hospitalization and death/recovery. Ehrlichiosis, anaplasmosis, and UUOA cases reported with CRFs were also combined into a single category for the majority of the analysis (unless otherwise noted) for comparison to the IHS data. Only cases with known race were used for the analysis; although 31% of CRF cases had missing race, the distribution of cases with and without specified race were similar in regards to sex, gender, and confirmed/probable case status. Incidence was not calculated for CRFs because they are not considered official case counts and only are submitted by the states on a voluntary basis. Median age at illness onset was compared by race using the Wilcoxon rank-sum test.35 Comparisons of clinical characteristics were analyzed using the χ2 test or Fisher's exact test (two-sided), as appropriate.37

IHS.

The IHS collects data on inpatient and outpatient visits for all eligible American Indian/Alaska Native (AI/AN) members of federally recognized tribes that use the IHS health care system; these data were used to determine the number of patients with a clinical diagnosis of ehrlichiosis or anaplasmosis on their inpatient and outpatient visit records from the IHS National Patient Information Reporting System.38,39 These data contain inpatient and outpatient visit data from IHS- and tribally operated hospitals, as well as community hospitals that have contracted with IHS or tribes to provide health care services to federally recognized eligible AI/AN persons in the United States.38,39 Approximately 1.6 million AI/AN persons are eligible for IHS-funded medical care in the United States.40 The IHS is composed of 12 regional administrative units (area offices) that are further grouped into geographic regions: East (Nashville), Northern Plains East (Bemidji), Northern Plains West (Aberdeen and Billings), Southern Plains (Oklahoma area), Southwest (Albuquerque, Navajo, Phoenix, and Tucson areas), Alaska and West (California and Portland areas for outpatient data only).40 The IHS California and Portland administrative areas in the West region were excluded from the inpatient analysis because neither had IHS nor tribally operated hospitals, California does not report contract health service inpatient data by diagnosis, and Portland has limited contract health services for inpatient care.40,41 Because of the absence of ehrlichiosis and anaplasmosis cases from the Alaska region, AI/ANs will be referred to as AIs unless otherwise noted.

Patient-based analysis was performed on inpatient and outpatient visit records for AIs with an ehrlichiosis diagnosis if a record had the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) code of 082.4 (Ehrlichiosis) as one of up to 15 diagnoses on the record.15 There is no ICD-9-CM code specific for anaplasmosis; however, before being renamed and reclassified as A. phagocytophilum, anaplasmosis was referred to as Human Granulocytic Ehrlichiosis and was included in the 082.4 code.1,5 As such, ehrlichiosis and anaplasmosis were combined into a single group for thisanalysis represented by the ehrlichiosis ICD-9-CM code. Records for inpatient and outpatient visits were linked by patient using IHS-encrypted unique identifiers (personal identifiers were not provided), allowing for the estimation of patient-based incidence of ehrlichiosis. For each patient, the first inpatient or outpatient visit with ehrlichiosis and anaplasmosis as a diagnosis during the study period was used in the analysis.

Incidence rates were calculated as the number of patients per 1,000,000 of the corresponding population. The annual IHS AI population denominator estimates were the IHS annual user populations for fiscal years 2001–2007 and the year 2000 as adjusted by the change in their service population to the fiscal year 2001 user population.42,43 The annual user population includes all AI/AN people who received IHS-funded healthcare services at least once during the previous 3 years. A test of trend by year was determined using Poisson regression analysis, and rates were compared using Poisson regression to determine RRs and 95% CIs.34

Results

NETSS.

For 2000–2007, a total of 5,364 cases of ehrlichiosis and anaplasmosis with a race group designation were reported through NETSS, including 90 cases among AIs. Of the 90 AI cases, 57 (63%) were E. chaffeensis, 21 (23%) were A. phagocytophilum, and 12 (13%) were classified as UUOA cases. The distribution of cases by disease type among all the other race groups combined showed significantly different proportions (44% E. chaffeensis, 43% A. phagocytophilum, 13% UUOA; P < 0.001). The AI E. chaffeensis cases were reported from the states of Oklahoma, Rhode Island, North Carolina, and Florida, whereas A. phagocytophilum cases were reported from the states of Connecticut, Massachusetts, Minnesota, New York, Oklahoma, and Wisconsin; all of the UUOA cases among AIs occurred in Wisconsin (Figure 1).

Figure 1.

Figure 1.

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County level incidence rates of (A) ehrlichiosis, (B) anaplasmosis and (C) undetermined, unspecified, or other agent cases among American Indians, 2000–2007, United States, National Electronic Telecommunications System for Surveillance.

During the study period, AIs had the highest average annual incidence of ehrlichiosis and anaplasmosis (4.0 cases per million; Table 1) compared with the other race groups (white: 2.9, [RR = 1.4, 95% CI = 1.1–1.7]; black: 0.4, [RR = 9.3, 95% CI = 7.1–12.2]; and Asian/Pacific Islander [A/PI]: 0.2 [RR = 16.6, 95% CI = 10.6–26.0]). When adjusting by state to control for confounding by geography, the RRs comparing AI to other race groups were similar to the unadjusted RRs for whites [adjusted RR (aRR) = 1.4, 95% CI = 1.2–1.8] and blacks [aRR = 9.2, 95% CI = 6.9–12.2] and lower for A/PI [aRR = 10.0, 95% CI = 6.3–15.6]. Annual incidence rates among AIs showed a significant increasing trend overall (P < 0.005) from 1.3 cases per million in 2000 to 7.9 in 2007, experiencing more than a 500% increase over the time period and with a particularly high rate among AIs in 2005 (Figure 2). The highest annual incidence for AIs occurred in 2005 (9.6 per million; Figure 2). The white, black, and A/PI race groups had similar significant increasing trends, but showed less of an increase than that seen for AIs (340%, 415%, and 130% increases, respectively; P < 0.05).

Table 1.

Comparison of incidence rates for ehrlichiosis and anaplasmosis cases among American Indians as reported by National Electronic Telecommunications System for Surveillance (NETSS), and the Indian Health Service (IHS), 2000–2007, United States

NETSS IHS
Rate (cases per million persons)
Overall incidence rate 4.0 14.9
Gender
 Male 5.3 18.6
 Female 2.8 11.5
Age group (years)
 0–4 2.0 6.4
 5–9 5.2 8.3
 10–19 2.6 8.5
 20–29 1.6 7.9
 30–39 1.2 11.9
 40–49 7.6 27.8
 50–59 5.9 30.3
 60–69 11.3 35.7
 70+ 5.6 27.4
Median age (years) 43 44
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Figure 2.

Figure 2.

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Average annual ehrlichiosis and anaplasmosis incidence rates* by race group, 2000–2007, United States, National Electronic Telecommunications System for Surveillance.

Among AIs, the incidence of ehrlichiosis and anaplasmosis for males was significantly higher than that for females (RR = 1.9, 95% CI = 1.2–2.9; Table 1); males had a consistently higher incidence compared with females across all race groups. The highest incidence among AIs occurred in the 60–69 year age group (11.3), whereas the lowest incidence occurred in the 20–29 (1.6) and 30–39 (1.2) year age groups (Table 1; Figure 3). Among the other race groups, the highest incidence occurred in the 60–69 year age group (except for among blacks which experienced the highest incidence in the 70+ year age group) and the lowest incidence occurred consistently in the youngest (0–4 year) age group. The median age among AIs (43 years; Table 1) was significantly lower than that of whites (54 years, P < 0.0001) and A/PIs (53 years, P < 0.001), and similar to that of blacks (46 years). Seasonally, the majority of cases among AIs occurred in the months of May through August (77.8%). This was similar to the seasonality of illness onset overall for cases with a race designation (the majority of cases occurred between May and August [74%]) and among the other race groups (Figure 4).

Figure 3.

Figure 3.

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Average annual ehrlichiosis and anaplasmosis incidence rates* by race and age group, 2000–2007, United States, National Electronic Telecommunications System for Surveillance.

Figure 4.

Figure 4.

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Proportion* of ehrlichiosis and anaplasmosis cases† by month of onset by race, 2000–2007, United States, National Electronic Telecommunications System for Surveillance.

CRFs.

For 2000–2007, 2,693 cases of ehrlichiosis and anaplasmosis were reported to CDC by CRFs; 75 of these cases were AIs. Of the AI cases, 53 (71%) were E. chaffeensis cases, 17 (23%) were A. phagocytophilum cases, and 5 (7%) were UUOA. This distribution of cases was different from whites and A/PIs, both of which had a lower percentage of E. chaffeensis (36% and 0%, respectively) and a higher percentage of A. phagocytophilum (41% and 46%, respectively) and UUOA (23% and 54%, respectively); blacks had a similar distribution of cases to AI (64% were E. chaffeensis cases, 21% were A. phagocytophilum cases, and 14% were UUOA). The smallest number of ehrlichiosis and anaplasmosis cases among AIs was reported in 2000 (N = 2), whereas the highest number of cases was reported in 2005 (N = 25). Of the AI cases reported by CRFs, only 5 (6.7%) of these were classified as confirmed cases based on the CDC case definition, which was lower than the percentage of confirmed cases (23.2%) among the other race groups combined (Table 2).

Table 2.

Selected characteristics of ehrlichiosis and anaplasmosis cases by race, Tick-borne Rickettsial Disease Case Report Forms, 2000–2007, United States

Characteristics* American Indians No. (%) All other races No. (%) Whites No. (%) Blacks No. (%) Asian/Pacific islanders No. (%)
Total 75 (100%) 2618 (100%) 2557 (100%) 48 (100%) 13 (100%)
Case status
 Confirmed 5 (6.7%) 607 (23.2%) 591 (23.1%) 11 (22.9%) 5 (38.5%)
 Probable 70 (93.3%) 2011 (76.8%) 1966 (76.9%) 37 (77.1%) 8 (61.5%)
Hospitalized
 Yes 33 (44.6%) 1073 (42.7%) 1033 (42.1%) 36 (76.6%) 4 (33.3%)
 No 41 (55.4%) 1439 (57.3%) 1420 (57.9%) 11 (23.4%) 8 (66.7%)
Outcome
 Recovered 52 (98.1%) 2370 (99%) 2315 (99.1%) 42 (95.5%) 13 (100%)
 Died 1 (1.9%) 23 (1%) 21 (0.9%) 2 (4.5%) 0 (0%)
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*

Information is not completely reported for all available characteristics.

The proportion of AI ehrlichiosis and anaplasmosis cases was higher among males (68%) than females (32%); males also had more cases than females in all other race groups. Among AI ehrlichiosis and anaplasmosis cases, the age group with the highest proportion of cases was the 40–49 year age group (31%); among whites the 60–69 year age group had the highest proportion of cases (21%) and among blacks the 40–49 year age group (22%) had the highest proportion of cases (cases were evenly distributed among A/PIs). The median age of cases at illness onset was 43 years among AIs (quartiles 18, 53) compared with the median age among whites (55, quartiles 41, 67; P < 0.0001). The median ages at onset were not significantly different for AIs compared with blacks and A/PIs.

Hospitalization was reported for 33 (44%) of the AI ehrlichiosis cases (Table 2). This proportion was similar to the proportion of hospitalized cases in each of the other race groups, except for blacks who had the highest proportion of hospitalized ehrlichiosis and anaplasmosis cases (75%; Table 2, P < 0.001). Among AIs, the age groups with the highest proportions of hospitalized cases were the youngest and the oldest age groups: 0–4 (66%), 50–59 (57%), 60–69 (62%), and 70+ years (100%). This distribution was similar to the other race groups.

One death caused by ehrlichiosis was reported among AIs (1.3%, Table 2). This was similar to the proportion of deaths reported among other race groups, except for blacks who experienced the highest case fatality (4.2%), although this was not significantly different. The AI ehrlichiosis death occurred in the 40–49 year age group. Among whites, most deaths occurred in the 40–49 (N = 4), 50–59 (N = 5), and 70+ (N = 7) year age groups; among blacks, two deaths occurred (one each in the 60–69 year and 70+ year age groups). No ehrlichiosis or anaplasmosis deaths were reported among A/PIs. Among AIs reporting immune status, 13% reported having immunosuppressive conditions including one case with cancer and another with arthritis; this is similar to the percentage of those reporting immunosuppressive conditions among whites (11%) and A/PIs (9%) and lower than that reported by blacks (28%, P < 0.005).

IHS.

For 2000–2007, 144 patients with an inpatient and/or outpatient visit with ehrlichiosis listed as a diagnosis were reported among AIs in the IHS health care system for an average annual incidence of 14.9 cases per million (Table 1). Of the 144 cases, 121 were seen as outpatients only, 15 were seen as inpatients only, and eight were seen as both inpatients and outpatients.

There was a significant increasing incidence trend from 2000 to 2007 (P < 0.005). The lowest annual incidence occurred in 2001 (3.8 per million) and the highest occurred in 2007 (34.1). The incidence was higher among males than among females (18.6 and 11.5, respectively; RR = 1.6, 95% CI = 1.2–2.3; Table 1). The lowest incidence occurred in the 0–4 year age group (6.4) and the highest occurred in the 60–69 year age group (35.7; Table 1). The median age of patients was 44 years (quartiles 23, 54).

Geographically, the highest incidence of ehrlichiosis occurred in the East region (80.4 cases per million), followed by the Northern Plains East region (68.5) and the Southern Plains region (35.2). The majority of cases occurred in the Southern Plains region (N = 73; 52%), all of which occurred in the state of Oklahoma. Seasonal distribution of patients based on the first hospital or outpatient visit showed that the majority of cases occurred between the months of June through August (57.6%). The majority of ehrlichiosis patients only had one hospital or outpatient visit associated with ehrlichiosis (68%).

Discussion

The ehrlichiosis and anaplasmosis rate is higher for AIs compared with other race groups and has increased at least 5-fold during 2000–2007. This increase is consistent with an increase of ehrlichiosis and anaplasmosis incidence experienced nationally over all race groups.44 This increasing incidence is, in part, attributed to changes in ehrlichiosis and anaplasmosis case definitions, new diagnostic assays, increased physician awareness, changes in the states that considered the diseases reportable, and improved state and local surveillance for tick-borne diseases.1,29,30,45 Some of the rate increase, particularly over the long term, is also possibly caused by changing ecology or climate, which results in varied vector and reservoir ranges and outdoor activities gaining popularity and residential growth expanding into rural geographic areas, thus increasing the interaction between humans and ticks.46–48 Possible explanations for the higher incidence of ehrlichiosis and anaplasmosis among AIs in particular might be social or anthropogenic factors such as living in more rural areas and engaging in recreational, social, or community activities that more frequently expose them to ticks, thus putting them at higher risk of infection with tick-borne rickettsial diseases.26

The epidemiology of ehrlichiosis and anaplasmosis infection among AIs also differs compared with other race groups. Data analyzed from NETSS show that infection among AIs has a different age distribution with higher incidence of cases in both young children and older age groups compared with the other race groups that experienced increasing incidence with age. The age distribution among AIs is also different compared with previous studies of the general United States population, which also examined confirmed and probable cases and found increasing incidence with age.49 Although not fully comparable to studies featuring actual clinical cases, sero-surveys and clinical summaries have suggested the possibility that the trends of increasing sero-positivity with age may be caused by increased antibody prevalence due to prior exposure,50 a greater susceptibility to recognizable disease in older age groups as opposed to higher infection rates (and potential misdiagnosis of non-specific febrile illness symptoms in older age groups),1 or the possible subclinical nature of disease in children.51 Active surveillance in endemic areas may clarify whether these reported differences between AIs and other races are an artifact of passive surveillance or whether these reported differences represent a true difference in the burden of disease by age and whether social and/or cultural factors may be contributing to this difference.

Geographic distribution is also an important factor in the epidemiology of ehrlichiosis and anaplasmosis infections by race, which is consistent with distribution of tick species and host preferences.1 The higher proportion of cases being reported as ehrlichiosis (> 60%) as opposed to anaplasmosis among AIs compared with the other race groups is likely linked because the majority of AI cases occurred in the state of Oklahoma and the IHS Southern Plains region, a region that hosts the largest AI population in the United States.52 This is also consistent with the geographical distribution of ehrlichiosis, which is more likely to occur in the southeastern and south-central United States, whereas anaplasmosis primarily occurs in the Northeast, the upper Midwest, and the Pacific coast.1

This study has also revealed significant differences among the surveillance systems examined in the study. The reported incidence using IHS data shows almost a 4-fold higher incidence compared with national surveillance reports for the same time period. This higher incidence among AIs in the IHS is subject to interpretation because of the reliance of the inpatient and outpatient visit data on ICD-9-CM clinical diagnoses for ehrlichiosis, which are limited by possible diagnostic miscoding and lack of laboratory verification.53,54 However, the IHS inpatient and outpatient visit data is the only source of data that has both direct and contract health service visits for AIs using the IHS health care system and is often the only source of health care for many rural AIs.55,56 Furthermore, studies have shown that misclassification of race and ethnicity in national surveillance data is a significant issue, particularly for minority groups such as AIs, whereas only members of federally recognized tribes are included in IHS data.57–60 In particular, one study of race using NETSS data has shown that because of access to care issues and the requirement for cases classified as confirmed or probable ehrlichiosis and anaplasmosis to have accompanying laboratory evidence, cases among whites are more likely to be reported or confirmed than other race groups; thus cases for AIs are likely being underreported via NETSS and CRF systems because of racial misclassification and lack of confirmatory testing.61 Other limitations of the IHS data include that the population denominator used to calculate the incidence is the number of AI/AN persons who are eligible to use and have recently used the IHS health care system and may not include all AI/AN persons who seek medical consultation. The AIs in the IHS analysis are not representative of all self-identified AIs in the United States.

The lower incidence reported from national surveillance systems could also be caused by the under-reporting or misclassification of ehrlichiosis and anaplasmosis as a result of the non-specific nature of its clinical manifestations and its similar presenting symptoms to other tick-borne diseases including Rickettsia parkeri and RMSF that occur in the same geographical areas. A study from North Carolina found that the serology of febrile patients with a history of tick bites showed equal likelihood of exposure to ehrlichiosis, anaplasmosis, and RMSF.62 Studies have also shown variable cross-reactivity among E. chaffeensis, E. ewingii, and A. phagocytophilum on serologic assays, resulting in missed diagnoses and an underestimate of the true burden of disease.14 In particular, the high number of anaplasmosis cases reported by NETSS among AI persons in Oklahoma in this study is more likely to be caused by E. chaffeensis cases that were tested incorrectly with A. phagocytophilum serologic tests, as this is outside the expected geographic range of the pathogen and is known to be a highly endemic area for ehrlichiosis. In addition, national surveillance systems for ehrlichiosis and anaplasmosis rely on passive reporting of cases for its surveillance.49,62 A study reporting rates from active surveillance in Missouri, which is endemic for ehrlichiosis, showed rates 10–100 times higher than those reported by passive surveillance.63 Furthermore, the rates of ehrlichiosis and anaplasmosis for AIs reported by NETSS may be lower than those reported by IHS because certain states did not consider the disease reportable for certain years; this is particularly relevant for non-reporting states in which there is a large population of AIs.

Tick-borne Rickettsial Disease CRFs provide a more stringent assessment of the confirmed and probable cases because more laboratory data accompanies the report; however, states are not mandated to report cases via this system making it an inappropriate choice to determine national incidence.49 Comparison of the hospitalization proportions between the CRFs (44%) and IHS (10%) shows additional differences in surveillance systems. The higher proportion of cases hospitalized reported by CRFs is likely because CRFs are submitted voluntarily by the states and do not represent official case counts. It is also likely that CRFs may be biased toward reporting more severe cases because of the type of information collected on the form, thus over-representing hospitalized ehrlichiosis and anaplasmosis cases. Further investigation is needed to validate ehrlichiosis and anaplasmosis cases reported by the national surveillance systems as well as those based on ICD-9-CM code designation to determine the most valid surveillance measure for these diseases.

The results from this study indicate that the risk of ehrlichiosis and anaplasmosis is higher in the AI population compared with other race groups and that specific public health and education programs targeting this high-risk population should be implemented to reduce infection. In addition, further assessment and investigation should be done to explore the epidemiologic differences between AIs and other race groups in terms of age distribution, geography, and proportion of ehrlichiosis cases versus anaplasmosis cases. Specifically, public health prevention messages should focus on both younger and older age groups to further prevent infection in these high-risk groups. Finally, as evidenced by the varied ehrlichiosis and anaplasmosis incidence between surveillance systems, it is important to continue maintaining and improving surveillance mechanisms and to foster communication and collaboration of the IHS surveillance with national surveillance systems so as to better monitor and meet the needs of this high-risk population group.

ACKNOWLEDGMENTS

We thank Barbara Strzelczyk (IHS) for technical assistance, the staff at the participating hospitals, and the IHS National Patient Information Reporting System. We also acknowledge the providers and health departments reporting to the NETSS and the Tick-borne Surveillance CRF systems.

Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Footnotes

Authors' addresses: Arianne M. Folkema, Division of High-Consequence Pathogens and Pathology (DHCPP), National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Centers for Disease Control and Prevention (CDC), Atlanta, GA, E-mail: AFolkema@cdc.gov. Robert C. Holman, DHCPP, NCEZID, CDC, Atlanta, GA. F. Scott Dahlgren and Jennifer H. McQuiston, Division of Vectorborne Diseases (DVBD), NCEZID, CDC, Atlanta, GA, E-mails: IOT0@cdc.gov and JMcQuiston@cdc.gov. James E. Cheek, Division of Epidemiology and Disease Prevention, Office of Public Health Support, Indian Health Service Headquarters, USDHHS, Albuquerque, NM.

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