Public Health Nursing Vol. 32 No. 5, pp.

517–531
0737-1209/© 2015 Wiley Periodicals, Inc.
doi: 10.1111/phn.12170

POPULATIONS AT RISK ACROSS THE LIFESPAN: CASE STUDIES

Using Spatial Disease Patterns and

Patient-Level Characteristics to Describe
Prevalence Elastic Behavior in
Treatment for Latent Tuberculosis
Infection (LTBI)
Kyle R. Fluegge, PhD, MPH,1,2,3
1
Agricultural, Environmental, and Development Economics, College of Food, Agriculture and Environmental Sciences and Division of
Epidemiology, College of Public Health, Ohio State University, Columbus, Ohio; 2Institute of Health and Environmental Research (IHER),
Cleveland, Ohio; and 3Department of Epidemiology and Biostatistics, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH,
44106.

Correspondence to:
Kyle R. Fluegge, Department of Epidemiology and Biostatistics, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH, 44106.
E-mail: kylefluegge@iher.org

ABSTRACT Objective: Individual adherence to a 9-month regimen of isoniazid (9INH) for treat-
ment of latent tuberculosis infection (LTBI) was hypothesized to reflect a prevalent elastic health
behavior pattern, or prevention behavior correlated with relevant disease burden. Method: Log-
rank tests were used to compare survival functions among raw prevalence tertiles for diseases
including TB, diabetes, and obesity. Own and cross-prevalence elasticities were calculated and spa-
tially characterized behavioral response to diseases that may impact TB re-infection and/or re-acti-
vation. Discrete choice models were used to assess the significance of the spatial elasticities
among an ethnically diverse clinic population of 552 patients in an urban American county in
2010. Results: Log-rank results revealed a statistical association between dropout and chronic
disease prevalence (p < .01), but not TB prevalence (p = .13). Discrete choice models incorporat-
ing spatial elasticities and controlling for patient- and treatment-level characteristics demonstrated
significant associations with adherence (p < .01), an effect robust to various alternative treatment
definitions. Conclusion: Individual LTBI adherence tracks a prevalence elastic pattern that may repre-
sent a potential risk for re-infection and re-activation.

Key words: adherence, diabetes, isoniazid, latent tuberculosis infection, prevalence elasticity,
rifampin.

Background tuberculosis infection (LTBI), some of whom will

Tuberculosis (TB) is a major global health concern.
In 2010, there were 8.8 million worldwide incident
cases (World Health Organization, 2011). The Cen-
ters for Disease Control and Prevention (CDC) esti-
mates that a third of the world’s population is
infected with Mycobacterium tuberculosis (Centers
for Disease Control and Prevention [CDC] (2012).
This constitutes a large pool of patients with latent
go on to develop active disease if not treated (Hors-
burgh, 2004). Complete treatment with 9 months
of isoniazid (9INH) provides between 70% and
90% protection against re-activation (Thompson,
1982), although shorter, efficacious alternatives do
exist (Shepardson et al., 2013; Sterling et al., 2011).
However, completion rates have been as low as
20%, with most individuals dropping out of therapy

517
518 Public Health Nursing Volume 32 Number 5
after the first month (Horsburgh et al., 2010). The
questions of relevance in this paper are (1) whether
LTBI adherence follows a prevalence elastic behav-
ior pattern, and (2) if so, what does this mean for
the pharmacotherapy options used by public health
nurses to treat LTBI?
Patient compliance with medication has long
been studied to understand how to improve adher-
ence with medications for both chronic and acute
conditions. The only consistent conclusion is that
there are no indicators that routinely predict nonad-
herence (Morris & Schulz, 1992; Vermeire, Hearn-
shaw, Van Royen, & Denekens, 2002).
Nonadherence has been described in terms of correl-
ative associations to a patient’s fixed characteristics,
including demographic factors such as age, sex, race,
ethnicity, occupation, income, education, and their
interaction. Sumartojo (1993) noted these demo-
graphic variables are not inherently causal and not
responsive to intervention by health care providers.
Most of the current literature on LTBI adher-
ence focuses on static patient qualities. A Spanish
study of LTBI adherence concluded that being male
or having an immigration status of less than
5 years were associated with lower odds of LTBI
treatment completion (Anibarro et al., 2010). Ailin-
ger, Moore, Nguyen, and Lasus (2006) noted how
adherence did not depend upon the patient’s gen-
der, country of origin, languages spoken, age,
education, or years in the United States, findings
which were replicated (Dobler & Marks, 2012). It is
difficult to comprehend how useful these findings
are in a policy context to actually explain the
inclination to drop out from LTBI therapy.
To advance this research on adherence, the
author explored LTBI adherence to a 9INH regi-
men using a motivation of prevalence elasticity.
This theory posits that engagement in preventive
behavior changes as a disease becomes more or
less prevalent (Funk, Salath
e, & Jansen, 2010).
Elasticities are used to quantify the changes in dis-
ease prevalence. Elasticity in the current context
refers to the measurement of how sensitive one
variable, such as LTBI adherence, is to a change
in another, such as the current TB burden and
other diseases that may affect that TB burden. A
negative (positive) elasticity suggests demand for
prevention of TB via LTBI treatment wanes
(grows) as the TB disease burden (or burden of
disease associated with TB) increases.
September/October 2015
Two disease pathways are considered, both of
which depend on patient behavior. The first is a
primary infection pathway, by which next period
TB prevalence may change as a function of increas-
ing incident infections, which is itself at least par-
tially dependent on current TB prevalence, but to a
larger extent dependent on immigration. The other
is a secondary infection pathway, by which next
period TB prevalence may fluctuate as a
consequence of current re-activations of dormant
infections.
The first pathway is operationalized principally
through examination of the importation of LTBI
cases via immigration. From 1970 to 2000, the dis-
parity in prevalence of LTBI among the nation’s
foreign-born population grew from three times
(35.9% to 12.6%) to over eight times greater (21.3%
to 2.5%) than that observed in the U.S.-born popu-
lation (Khan et al., 2008). This decline in LTBI
prevalence, either real or a result of unreported
incident cases (Bennett et al., 2008), occurred
despite the increase in the share of foreign-born
population in the United States during the same
time, increasing from 4.7% to 10.4% (Lollock,
2001). These statistics mirror the equally disparate,
albeit decreasing, trend in TB incidence among for-
eign-born patients in the United States (CDC,
2014).
The primary infection pathway may influence
TB disease prevalence in an unexpected manner.
Andrews et al. (2012) compared incidence rate
ratios among two groups of patients (with and
without LTBI) for progression to active TB. They
noted a 79% lower risk of progression to active dis-
ease among patients with a preexisting infection.
Such a perverse incentive to minimizing TB re-acti-
vation in the future may help support an alternative
hypothesis of patient behavior driven by a negative
elasticity (Auld, 2003, 2006), also known as
“rational fatalism.” Fluegge, Durcholz, and Barker
(2013) argued that in a global setting with TB ende-
micity, where neither LTBI testing nor treatment is
routinely practiced, the missing market for acquired
immunity imparts a reliance on one’s innate immu-
nity as the sole, albeit imperfect, form of protec-
tion. When re-locating to a country with an easily
accessible market for acquired immunity (and, by
correlation, reduced TB burden), the receipt of said
immunity provides high utility to the patient who
lived so long without it as opposed to patients who
 Fluegge: Prevalence Elastic Behavior and LTBI Treatment
did not. Thus, it is important to consider potential
nonmonotonicity in the primary infection pathway.
That is, foreign-born patients may respond
differently to current TB burden than domestic
patients. Previous work has indicated a concern by
immigrants themselves of the risks posed by their
own TB status (Shipp, Francis, Fluegge, & Asfaw,
2014), perhaps indicative of their awareness to TB
exposure in their country of origin.
The second pathway is operationalized via a con-
sideration of the convergence of TB with diabetes
mellitus, which has received attention as a catalyst
for concern in explaining the domestic TB burden
(Dooley & Chaisson, 2009). The findings for diabetes
may be relevant for immigrants from TB endemic
areas who come to the United States, where preva-
lence of diabetes is high and projected to escalate
even higher (Shaw, Sicree, & Zimmet, 2010). A Cana-
dian study investigating the risk of diabetes among
over a million immigrants showed a significant asso-
ciation between risk of diabetes and immigrants
from Asia, Latin America, and sub-Saharan Africa,
as compared to Western immigrants (Creatore et al.,
2010). One reason for this finding may be that the
incidence of diabetes in the developing world has
been increasing at rates faster than in the developed
world (Shaw et al., 2010). In addition, the mortality
rate from diabetes has declined such that more peo-
ple are living with the disease longer (Lipscombe &
Hux, 2007). Furthermore, recent research has indi-
cated that a family history of diabetes increases the
risk of prediabetes (Wagner et al., 2013), which is
itself a risk factor for diabetes (Tabak, Herder, Rath-
mann, Brunner, & Kivim€aki, 2012). Obesity is also a
known risk factor for the development of diabetes
(Sung, Jeong, Wild, & Byrne, 2012). The growth in
obesity, and by correlation diabetes, may have both
endogenous and contextual influences through social
networks and shared environments (Cohen-Cole &
Fletcher, 2008).
The secondary infection pathway may influence
TB disease prevalence as a consequence of this
growing diabetes epidemic. Stevenson et al. (2007)
found a statistically significant association between
diabetes and TB among an ethnically diverse
patient population. Their association varied from a
1.5-fold to a 7.8-fold increase in the risk of TB.
Jeon and Murray (2008) noted similar conclusions
in their synthesis of thirteen observational studies
to assess the influence of diabetes on TB re-activa-
519
tion. A cross-prevalence elasticity measures the
responsiveness of the demand for TB prevention to
a change in the prevalence of another disease that
may impart negative influence on the prevalence of
TB, including diabetes. A negative cross-prevalence
elasticity suggests that demand for TB prevention
increases (decreases) as the prevalence of diabetes
decreases (increases).
Given these pathways and a description of
hypothesized influences on TB prevalence, it is of
interest to note the associations between LTBI
treatment behavior and these relevant disease pat-
terns. To investigate, the author generated own and
cross-prevalence elasticities to determine how elas-
tic TB prevention is to disease patterns that could
impact re-infection and re-activation likelihood.
The author also assessed individual patient behav-
ior with discrete choice models to test the signifi-
cance of the elasticities. Results revealed (1)
nonmonotonicity in the primary infection pathway
for non-English speaking patients, (2) a spatially
nonuniform elasticity structure, although regions
with elastic own prevalence associations always had
elastic cross-prevalence impacts, and (3) a rejection
of the null hypothesis of prevalence inelastic behav-
ior, after controlling for patient characteristics. The
results provide insight to public health nurses.
There may be value in intra-professional collabora-
tion in treating not only TB and LTBI but also
conditions associated with its re-activation. Such
collaboration is necessary because shorter pharma-
cotherapy options do not eliminate the association
between individual adherence and the examined
prevalence elasticities.
Methods
The study sample consisted of patients presenting
to an urban public health clinic for LTBI treatment
during 2010. These patients received 9INH, unless
they experienced a side effect that warranted a dis-
continuation of this regimen. In that case, these
patients were transitioned to 4 months of rifampin
(transitional 4RIF). Patients were given medica-
tions monthly and determined to have completed
medication for each month if they returned to pick
up the proceeding month’s supply. Patients were
routinely assessed for INH toxicity via liver func-
tion tests (LFTs) and patient self-report of physical
symptoms.
520 Public Health Nursing Volume 32 Number 5
To describe patient-level characteristics,
patients were grouped by their dropout behavior,
described as vd. The first group included patients
who did not start treatment, denoted by v3 = 1 (i.e.,
highest degree of dropout). This group comprised
patients who did not return to the clinic for the
first refill. The second group included patients who
started but did not complete treatment (d = 2). The
final group consisted of patients who started and
completed treatment, denoted by v1 = 1. Tests of
ANOVA and chi-square tests were used to assess
the differences among adherence groups for contin-
uous and categorical variables, respectively.
The number of TB cases in the urban county of
interest was summed over the years 2009 and 2010
to calculate a period prevalence. The LTBI cases
were only for the year 2010. For all zip codes within
the county, the count data for TB and LTBI cases
obtained from the public health clinic were used
with population statistics to calculate the period
prevalence of TB by zip code. Zip code level data of
diabetes and obesity prevalences were accumulated
for the year 2010 (National Minority Quality Forum,
2013). Log-rank tests were performed to assess the
association of these raw prevalences with adherence.
Own (ETB) and cross-prevalence elasticities (ED
and EO for diabetes and obesity, respectively) were
calculated as the ratio of percent change in spatial
prevention uptake to percent change in disease
prevalence. Prevention uptake is a proportion of
the number of patients completing LTBI treatment
in a zip code divided by the total number of LTBI
patients in the same zip code. The referent zip code
was uniquely identified for each disease and
defined as the zip code with the greatest prevalence
of said disease. For example, the referent zip code
for own prevalence elasticity was the zip code with
the greatest TB prevalence. By comparison, every
other zip code would have a lower disease burden.
In this case, negative elasticities suggest a greater
population demand for TB prevention. Demand for
TB prevention was considered relatively inelastic
when the percentage change in prevention uptake
was less than the percentage change in prevalence
(1 > ETB, ED, EO > – 1) and relatively elastic when
the percentage change in prevention uptake was
greater than the percentage change in prevalence
(ETB, ED, EO < – 1, ETB, ED, EO > 1).
A series of discrete choice models was used to
investigate individual LTBI adherence. The simple
September/October 2015
probit model examined what factors influenced the
dropout decision:
X
a1
v1 ¼
1 þ 1i x1ij þ 1 eD
1j
þ 2 y1j þ 3 c1j þ u1j ; ð1Þ
i
where v1 is a binary indicator of treatment comple-
tion (did or did not complete LTBI treatment), x1ij
includes a1 variables describing patient j (binary
indicators of diabetes status, family history of dia-
betes, and obesity status, and number of years since
immigration for foreign-born patients), eD 1j
with
D = TB, D, O (i.e., TB, diabetes, obesity) is one of
three spatial-level prevalence elasticities, y1j denotes
a binary indicator of side effects, c1j is the total cost
to treat, and u1j is the random error. The estimated
parameters are b1i, /1, /2, and /3.
Alternate specifications include the bivariate
probit, ordered probit, and panel probit models. The
bivariate probit model consists of two regressions
which distinctly explain starting and completing
treatment, denoted by v3 and v1, respectively. The
correlation between the errors of these sequential
decisions is given by q (rho). This statistic is used to
determine whether there are one or more variables
that are not in the model that make patients who
start less likely to complete therapy. A nonsignificant
q indicates there are no such variables.
The ordered probit selection rule accommo-
dates three dropout categories (d = 1, 2, 3) in a sin-
gle regression (i.e., dependent variable is vd as
opposed to v1). The categories reflect degree of
dropout: d = 1 denotes adherent patients, d = 2
describes patients who started but did not complete
treatment, and d = 3 characterizes patients who did
not officially start therapy.
A panel (i.e., random effects) probit model is
also presented with dependent variable of vd,t,
where binary dropout is determined at each treat-
ment visit, t. This model allows for correlated bin-
ary outcomes when assessing adherence
longitudinally (Gibbons & Hedeker, 1994). With the
exception of the first regression in the bivariate
probit model, the independent variables in these
additional regressions are the same as that specified
in Equation 1.
Finally, the robustness of the elasticities’ asso-
ciation with LTBI adherence was analyzed by
changing the treatment. That is, the dependent
variable was altered to reflect adherence to the fol-
lowing three modified treatment regimens: (1) only
 Fluegge: Prevalence Elastic Behavior and LTBI Treatment
9INH (excludes any 4RIF prescribed), (2) only
6 months of isoniazid (6INH), and (3) 6 months of
isoniazid with 4 months of transitional rifampin (if
needed). The first alternative categorized patients
who transitioned to 4RIF as nonadherent. Adher-
ence for the second occurred for any patient who
completed at least 6INH. Patients transitioning to
4RIF before completing 6INH were counted as
nonadherent. The last alternative defined adherence
as completing at least 6INH or 4RIF.
Clinic data were collected on-site through indi-
vidual record review of all sample patients. Institu-
tional review board approval was granted by the
local state university in 2011. All analysis was com-
pleted with Stata 11.1 (StataCorp, 2009) and ArcGIS
10.1 (ESRI, 2011).
Results
Table 1 gives the descriptive statistics of the clinic
sample. Each variable is denoted as continuous (C)
or binary (B). The number of months in which
medication was dispensed did not mirror the num-
ber of clinic visits. Some patients (N = 10) who
consumed less than a month’s medication experi-
enced a side effect and were subsequently moni-
tored for toxicity, but ultimately chose not to
continue with therapy once the issue was resolved.
Nine patients reported a side effect and
subsequently dropped out, but did not receive any
additional treatment for the incident.
At least 75% of patients within each adherence
category were foreign-born. Language is considered
the strongest single predictor of acculturation
among foreign-born patients, regardless of the eth-
nicity of the immigrant (Arcia, Skinner, Bailey, &
Correa, 2001; Jiang, Green, Henley, & Masten,
2009; Marin & Gamba, 1996). In the current study,
LTBI patients stated at intake their preferences for
language communication. Patients who did not have
a stated preference for English were categorized as
non-English-speaking patients. A particular subset
of less acculturated foreign-born patients, including
patients without English proficiency (p < .05) and
fewer years in the United States since immigrating
(p < .05), were the most likely to complete therapy.
Table 2 presents the raw prevalence statistics
and the respective prevalence elasticities. For space,
only zip codes with a nonzero TB prevalence are
listed. For each of the three diseases of interest, the
521
zip code with the highest TB burden also had the
highest prevalence of diabetes and obesity. Thus,
the referent zip code for all prevalence elasticities
was the same. Among 28 zip codes with at least
one reported TB case in 2009 or 2010, 26 zip codes
experienced a prevalence that was greater than the
2010 national rate of 3.6 cases per 100,000 people
(CDC (2011). The largest prevalence rates were
above 40 cases per 100,000. Five zip codes
exhibited uniformly elastic population responses to
disease prevalence (3, 12, 13, 14, and 21).
Figure 1 gives the color-coded schematic of the
period prevalences for TB (top map [Butler, perso-
nal communication, 2010]) and LTBI (bottom
map). For LTBI (TB), the darker shades indicate a
greater prevalence. Figure 2 displays the prevalence
rates of obesity and diabetes within the county in
2010. The correlations between prevalence rates
were high. Among zip codes with a nonzero TB per-
iod prevalence, the correlations between TB and
diabetes and TB and obesity were 0.73 (p < .0001)
and 0.68 (p < .0001), respectively.
Log-rank tests for equality of survivor functions
were used to determine whether patient dropout
was associated with any of these relevant spatial
disease patterns. Comparisons of survivor functions
were used to account for the multiple relocations of
many patients throughout the treatment process,
which impacts their exposure to disease distribu-
tions. For each disease of interest, tertiles of preva-
lence comprised the different survivor functions.
The tests revealed mixed results: TB rates were not
associated with dropout (chi-squared statistic of
4.05, p = .13); diabetes rates were associated with
dropout (chi-squared statistic of 11.79, p < .01);
obesity rates were associated with dropout (chi-
squared statistic of 12.67, p < .01). Tests of trend
results provided similar findings for TB rates (chi-
squared statistic of 4.05, p = .13), diabetes rates
(chi-squared statistic of 6.58, p = .01), and obesity
(chi-squared statistic of 4.24, p = .04).
Subset analyses revealed numerous interesting
findings. When examined solely on the occurrence
of treatment nonstarters, the results were signifi-
cant (TB: chi-squared statistic 11.52 with p < .01;
obesity: chi-squared statistic 7.93 with p = .02; and
diabetes: chi-squared statistic 11.87 with p < .01).
In addition, investigating the associations among
only non-English-speaking patients revealed
nonmonotonicity in the dropout outcome for TB
 522

TABLE 1. LTBI Patient Characteristics by Dropout Status

v3 = 1 (N = 96) v2 = 1 (N = 154) v1 = 1 (N = 302)

N Mean [Min, Max] SD N Mean [Min, Max] SD N Mean [Min, Max] SD
(C, B) Patient-levela
Public Health Nursing

(C) Age 96 39.31 [18, 81] 14.38 154 38.85 [20, 73] 12.14 302 39.74 [18, 88] 14.82
(B) Male* 96 0.59 [0, 1] 0.49 154 0.45 [0, 1] 0.50 302 0.52 [0, 1] 0.50
(C) Years of Education† 94 10.91 [0, 16] 4.65 154 10.73 [0, 18] 4.33 293 9.42 [0, 16] 5.31
(B) Insurance: None† 96 0.64 [0, 1] 0.48 154 0.56 [0, 1] 0.50 302 0.47 [0, 1] 0.50
(C) Distance from clinic 96 8.60 [0.45, 19.2] 4.45 153 8.36 [0.3, 23.9] 4.24 302 9.10 [0.19, 18.6] 3.37
(B) Patient has diabetes 96 0.03 [0, 1] 0.17 154 0.05 [0, 1] 0.21 302 0.08 [0, 1] 0.27
Volume 32

(B) Family history diabetes 96 0.18 [0, 1] 0.38 154 0.26 [0, 1] 0.44 302 0.20 [0, 1] 0.40
(B) Patient is obese 96 0.26 [0, 1] 0.44 154 0.32 [0, 1] 0.47 302 0.26 [0, 1] 0.44
(C) Years in United States, 96 4.44 [0, 31] 6.88 154 5.38 [0, 29] 6.68 302 3.72 [0, 40] 6.52
foreign-born‡
(B) Patient foreign-born* 96 0.77 [0, 1] 0.42 154 0.75 [0, 1] 0.44 302 0.84 [0, 1] 0.37
Number 5

(B) Has English fluency† 96 0.63 [0, 1] 0.49 154 0.53 [0, 1] 0.50 302 0.36 [0, 1] 0.48
(B) Previous LTBI patient 96 0.09 [0, 1] 0.29 154 0.12 [0, 1] 0.33 301 0.10 [0, 1] 0.30
(B) Incidence of side effects (SE)† 96 0.20 [0, 1] 0.40 154 0.35 [0, 1] 0.48 302 0.48 [0, 1] 0.50
(C) Costs of SE|SE = 1† 6 88.51 [0,253.43] 88.58 46 232.45 [90,653.3] 120.8 136 349.64 [180,800] 108.5
(C) Total cost† 96 55.36 [0,253.43] 26.15 154 157.26 [46.81, 653.29] 92.91 302 288.86 [143.58, 880.25] 97.42
(B) Rifampin use† 96 0.31 [0, 1] 0.17 154 0.04 [0, 1] 0.19 302 0.11 [0, 1] 0.31
(C, B) Spatial-levelb
(C) TB period prevalence (PP) 96 14.56 [0, 43.2] 11.09 154 13.46 [0, 43.2] 11.09 302 13.06 [0, 43.2] 9.36
(C) TB PP 9 no English 96 6.39 [0, 43.2] 10.74 154 5.62 [0, 42.4] 8.60 302 8.24 [0, 43.2] 9.21
preference‡
(C) Obesity prevalence 96 37.98 [27.54, 46.94] 4.44 154 37.57 [27.54, 44.7] 4.76 302 37.15 [27.54, 46.94] 4.17
September/October 2015

(C) Diabetes prevalence 96 12.45 [7.63, 19.43] 284 154 12.22 [7.29, 17.19] 2.83 302 11.89 [7.29, 19.43] 2.43

a
“C” refers to continuous variable. “B” refers to binary variable.
b
The disease distributions are based on the patient’s report of their residence at treatment initiation.
Chi-square (categorical) and one-way ANOVA (continuous): †p < .01, ‡p < .05, *p < .10.
 Fluegge: Prevalence Elastic Behavior and LTBI Treatment 523

TABLE 2. Prevalence Elasticities

Zip 2010 TB Rate LTBI Rate Prevention Diabetes Obesity

Code Population Per 100K per 100K Uptake Prevalence Prevalence ETB ED EO
1 8,108 43.2 61.67 0.400 0.1943 0.4694
2 27,123 42.4 121.67 0.364 0.167 0.447 4.91 0.65 1.91
3 21,600 34.7 41.67 0.667 0.1678 0.4451 3.39 4.89 12.88
4 50,737 18.7 63.07 0.500 0.1108 0.3552 0.44 0.58 1.03
5 45,144 16.6 33.23 0.533 0.1255 0.3848 0.54 0.94 1.85
6 46,347 16.2 92.78 0.419 0.116 0.3734 0.07 0.12 0.23
7 38,699 14.2 273.91 0.660 0.1295 0.3915 0.97 1.95 3.92
8 24,650 14.2 24.34 0.167 0.0795 0.2986 0.87 0.99 1.60
9 42,104 13.1 16.63 0.571 0.1092 0.3512 0.62 0.98 1.70
10 12,272 12.2 211.86 0.308 0.1943 0.4445 0.32 4.35
11 12,790 11.7 46.91 0.333 0.114 0.3422 0.23 0.40 0.62
12 30,444 11.5 82.12 0.720 0.1215 0.3804 1.09 2.14 4.22
13 51,836 10.6 30.87 0.750 0.1012 0.3514 1.16 1.83 3.48
14 33,847 10.3 23.64 0.750 0.0988 0.3495 1.15 1.78 3.43
15 37,626 9.3 18.60 0.571 0.0763 0.2793 0.55 0.71 1.06
16 42,201 8.3 59.24 0.520 0.1306 0.405 0.37 0.92 2.19
17 18,551 8.1 75.47 0.714 0.0794 0.2924 0.97 1.33 2.08
18 19,685 7.6 238.76 0.553 0.1078 0.3598 0.46 0.86 1.64
19 21,340 7 65.60 0.571 0.1404 0.4185 0.51 1.54 3.95
20 22,727 6.6 39.60 0.556 0.0976 0.3393 0.46 0.78 1.78
21 23,258 6.4 8.60 1.000 0.0768 0.2924 1.76 2.48 3.98
22 24,989 6 16.01 0.250 0.0788 0.2833 0.44 0.63 0.95
23 27,366 5.5 40.20 0.636 0.126 0.376 0.68 1.68 2.97
24 27,698 5.4 28.88 0.750 0.0939 0.3363 1.00 1.69 3.09
25 35,495 4.2 11.27 0.500 0.1286 0.3612 0.28 0.74 1.08
26 38,493 3.9 7.79 0.667 0.0797 0.2896 0.73 1.13 1.74
27 54,017 2.8 18.51 0.600 0.0815 0.303 0.53 0.86 1.41
28 58,424 2.6 11.98 0.571 0.091 0.3349 0.46 0.81 1.50
Range [3.39, 4.91] [4.89, 0.99] [12.88, 4.35]

(chi-squared statistic 5.05 with p = .08) and obesity
(chi-squared statistic 6.22 with p = .04), but not
diabetes (chi-squared statistic 3.27 with p = .19).
Table 3 reports the marginal effects of the most
relevant variables. The left side of the table lists the
five probit models. For each model, three separate
regression sets were analyzed to avoid issues with
multicollinearity. For each regression set, three
parameter estimates are shown: the elasticity mea-
sure, a binary indicator of the patient’s diabetic sta-
tus, and binary indicator of family history of
diabetes. Other variables included in the regres-
sions (but not reported) were a binary indicator of
side effects, total cost to treat, years in the United
States since immigration for foreign-born patients,
and patient’s obesity status. For all elasticity mea-
sures, results indicated an increasingly elastic com-
munity response to prevention was significantly
associated with individual patient dropout. In the
own TB prevalence elasticity of the first regression,
the increased probability of dropout ranged from
0.03 to 0.12 per unit increase in elasticity. The
comparable ranges for the cross prevalence elastici-
ties were 0.05 to 0.24 for diabetes and 0.02 to 0.11
for obesity.
Marginal effects for continuous variables mea-
sure the instantaneous rate of change on the drop-
out probability. If TB elasticity increased by one,
the probability of dropout (using the simple probit
model) would increase by 0.08. The second and
third zip codes listed in Table 2 showed an own
prevalence difference of over 8, which constitutes a
0.64 increase in the probability of dropout in the
former. This is significant considering the two zip
codes border one another. Similarly, the second
and seventh zip codes share a border; the increase
in dropout probability in the second is about 0.48.
The marginal effect of being diabetic was 0.27,
which means for two hypothetical patients with
average values for other variables, the predicted
524 Public Health Nursing Volume 32 Number 5
Figure 1. Prevalence of TB per 100,000 Population (Top), Prevalence of LTBI per 100,000 Popula-
tion (Below), By Zip Code
probability of dropout was 0.27 less for a diabetic
patient than a nondiabetic patient.
The second to last model in the table, labeled
the adjusted simple probit, repeated the simple pro-
bit model, with the addition of other covariates that
previous researchers have identified as having influ-
ence on the dropout likelihood. These variables
included gender, patient age, education (in years),
previous LTBI patient (yes = 1), whether patient
had insurance (= 1), and the distance (in miles)
from clinic. The results suggested little deviation
from the original model. The estimate for family
history of diabetes was slightly attenuated, but mar-
ginally significant in predicting dropout (b = 0.14,
p = .055).
These effects were generally robust across the
other probit specifications, with the exception of
the panel probit. This model included dynamic
variations for the elasticity measures, the cost
September/October 2015
figures, and the incidence of side effects. The pri-
mary reason for use of the panel probit was to dis-
tinguish spatial effects that change over time while
simultaneously controlling for individual character-
istics. Ninety-four patients re-located during ther-
apy (67% of that total re-located to a different zip
code). Furthermore, the dynamic data on side
effects, cost to treat, and distance from clinic
potentially captured intra-individual variation in
dropout not present in the cross-sectional models.
For this model, all elasticities increased in
magnitude. Both patient-level indicators with
respect to diabetes lost significance. Robustness
checks revealed these estimates were not sensitive
to the number of integration points chosen. To
assess the utility of the panel approach, the panel-
level variance was computed. The null hypothesis is
that the proportion of the total variance contributed
by the panel-level variance component was zero.
 Fluegge: Prevalence Elastic Behavior and LTBI Treatment 525

Figure 2. Prevalence of Diabetes per 100,000 Population (Top) and Obesity per 100,000 Population
(Below), By Zip Code

Calculation of the proportion dictated a rejection of
the null hypothesis for each regression set: 0.47
(p < .001), 0.36 (p < .01), and 0.38 (p < .01) for
regression sets 1, 2, and 3, respectively. Thus, the
panel probit was the preferred model.
The panel model in Table 3 incorporated a
binary indicator of rifampin use along with other
static patient characteristics, including patient
education and gender into the panel analysis.
Rifampin was used as the transitional treatment
for patients who could not tolerate the 9INH regi-
men. Its use was intended to reduce dropout
among a subset of patients who experienced side
effects. Although use of rifampin did significantly
reduce dropout as expected (marginal b = 1.90,
p < .001 for regression set #1), it did not alter the
elasticity estimates. Thus, the associations of the
population-level elasticity measures with individual
dropout were robust to the alternative pharmaco-
therapy regimen given. Other static characteristics
significantly explained patient behavior (not
reported in Table 3): male patients exhibited sig-
nificantly greater dropout (for regression set #1,
b = 0.31, p = .03), whereas each additional year of
education also exacerbated dropout (for regression
set #1, b = 0.01, p = .01). However, the elasticity
estimates were generally greater in magnitude than
these static effects.
 526
TABLE 3. Probit Models: Marginal Effects on (Degree of) Dropout

Regression set #1 Regression set #2 Regression set #3

Variables Variables Variables
Family
Patient has Family history Patient has Family history Patient has history
Model ETB diabetes diabetes ED diabetes diabetes EO diabetes diabetes
*** ** ** *** ** *
Simple 0.08 0.27 0.15 0.12 0.28 0.14 0.05*** 0.28** 0.14*
probita (0.03) (0.07) (0.07) (0.03) (0.07) (0.08) (0.01) (0.07) (0.08)
Public Health Nursing

N = 547, Log-likelihood = 183.56 N = 547, Log-likelihood = 179.15 N = 547, Log-likelihood = 180.50

Ordered 0.03** 0.20*** 0.10** 0.05*** 0.20*** 0.09* 0.02*** 0.21*** 0.09*
probit (0.02) (0.07) (0.05) (0.02) (0.06) (0.05) (0.008) (0.06) (0.05)
N = 547, Log-likelihood = 301.70 N = 547, Log-likelihood = 299.44 N = 547, Log-likelihood = 300.19
Volume 32

Bivariate 0.04*** 0.17*** 0.09** 0.07*** 0.17*** 0.08* 0.03*** 0.17*** 0.08*
probitb (0.02) (0.06) (0.04) (0.02) (0.05) (0.04) (0.009) (0.06) (0.04)
N = 547, Log-likelihood = 332.77 N = 547, Log-likelihood = 327.75 N = 547, Log-likelihood = 329.56

Adj. simple 0.08*** 0.25*** 0.14* 0.12*** 0.27*** 0.14* 0.05*** 0.27*** 0.14*
Number 5

probitc (0.03) (0.08) (0.07) (0.03) (0.08) (0.08) (0.01) (0.08) (0.08)
N = 536, Log-likelihood = 173.98 N = 536, Log-likelihood = 170.00 N = 536, Log-likelihood = 171.08

Panel (RE) 0.11*** 0.14 0.07 0.23*** 0.12 0.10 0.10*** 0.13 0.10
probitd (0.04) (0.29) (0.16) (0.05) (0.26) (0.14) (0.02) (0.27) (0.14)
N = 3250, Log-likelihood = 702.32 N = 3250, Log-likelihood = 693.94 N = 3250, Log-likelihood = 695.10

a
Additional covariates include binary indicator of side effects, total cost to treat, years in the United States since immigration, and patient’s own obesity sta-
tus.
b
Only second regression results presented. Second regression contains same covariates as simple probit. First regression included predictors for side effects
within first month (yes = 1), total cost to treat, and elasticity measure. Residual correlations were not significant: q1 = .22 (p = .42); q2 = .32 (p = .31);
September/October 2015

q3 = .31 (p = .31).
c
Additional covariates include gender (male = 1), patient age, education (in years), previous LTBI patient (yes = 1), patient has no insurance at treatment initi-
ation (=1), and distance from clinic when starting treatment.
d
RE = random effects. Additional dynamic covariates (not reported in table) include month of treatment, total cost, the incidence of side effects, the cumula-
tive number of side effects reported throughout therapy, distance from the clinic, use of rifampin, as well as other static variables included in the adj. simple
probit model.
***p < .01, **p < .05, *p < .10; Robust standard errors reported in parenthesis; Marginal effects at means reported in brackets. The marginal effects are calcu-
lated via the delta method. The marginal effects for the ordered probit model are calculated for only the probability of v2 = 1 (i.e., started and dropped out).
Marginal effects are calculated at the means for continuous variables and at zero for binary variables.
TABLE 4. Sensitivity Analyses

Alternative treatment protocol

9INH alone 6INH alone 6INH + 4RIF
Model ETB ED EO ETB ED EO ETB ED EO
Simple probit 0.06*** 0.10*** 0.04*** 0.05** 0.09*** 0.04*** 0.06* 0.11*** 0.05***
(0.02) (0.02) (0.01) (0.02) (0.02) (0.01) (0.03) (0.03) (0.01)
N = 545 N = 545 N = 545 N = 545 N = 545 N = 545 N = 547 N = 547 N = 547
LL = 293.3 LL = 288.1 LL = 289.4 LL = 284.7 LL = 278.9 LL = 280.0 LL = 168.7 LL = 163.2 LL = 164.3
Ordered probit 0.02** 0.03*** 0.01*** 0.02** 0.02** 0.01** 0.02 0.05* 0.02*
(0.01) (0.01) (0.004) (0.01) (0.01) (0.004) (0.02) (0.03) (0.01)
N = 545 N = 545 N = 545 N = 545 N = 545 N = 545 N = 547 N = 547 N = 547
LL = 452.7 LL = 450.6 LL = 451.1 LL = 427.4 LL = 426.9 LL = 427.1 LL = 231.0 LL = 228.6 LL = 229.2
Bivariate probit 0.05*** 0.09*** 0.04*** 0.04*** 0.08*** 0.03*** 0.03* 0.06*** 0.03***
(0.02) (0.02) (0.01) (0.02) (0.02) (0.01) (0.02) (0.02) (0.01)
N = 545 N = 545 N = 545 N = 545 N = 545 N = 545 N = 547 N = 547 N = 547
LL = 428.9 LL = 422.3 LL = 424.2 LL = 420.0 LL = 412.8 LL = 414.4 LL = 317.7 LL = 311.4 LL = 313.0
Adj. simple probit 0.06*** 0.09*** 0.04*** 0.05** 0.09*** 0.04*** 0.05* 0.11*** 0.05***
(0.02) (0.02) (0.01) (0.02) (0.02) (0.01) (0.03) (0.03) (0.01)
N = 545 N = 545 N = 545 N = 545 N = 545 N = 545 N = 547 N = 547 N = 547
LL = 280.42 LL = 275.8 LL = 276.7 LL = 276.4 LL = 271.0 LL = 271.8 LL = 163.9 LL = 158.5 LL = 159.5
Panel (re) probit 0.17* (0.10) 0.30*** (0.10) 0.14*** 0.24* (0.14) 0.73*** (0.23) 0.30*** (0.10) 0.12** 0.26*** 0.12***
(0.05) (0.05) (0.06) (0.02)
N = 3107 N = 3107 N = 3107 N = 2326 N = 2326 N = 2326 N = 2461 N = 2461 N = 2461
LL = 709.6 LL = 703.6 LL = 704.4 LL = 613.0 LL = 608.3 LL = 609.2 LL = 619.2 LL = 609.4 LL = 610.6

***p < .01, **p < .05, *p < .10.

Fluegge: Prevalence Elastic Behavior and LTBI Treatment
527
528 Public Health Nursing Volume 32 Number 5
Table 4 reports the results of the robustness
checks for the association between the defined elas-
ticities and adherence. The first column of each
regression set in Table 3 is repeated in Table 4,
only modifying the adherence to the alternative reg-
imen as specified previously. The estimates largely
agree across alternative treatment scenarios and are
consistent with the estimates presented in Table 3
using the 9INH with transitional 4RIF protocol (if
needed).
Discussion
In this paper, adherence to an LTBI regimen with
9INH and transitional 4RIF was explored using
both spatial- and patient-level variables that are
associated with the probability of TB re-infection
(via TB prevalence) and re-activation (via diabetes
and obesity prevalence). Log-rank tests were pur-
sued to investigate the association of patient adher-
ence with raw prevalence statistics. To mitigate
nonmonotonicity issues identified in the log-rank
analysis, elasticities were then calculated to discern
the association between population-level prevention
uptake and disease prevalence. Finally, discrete
choice models assessed the robustness of the elas-
ticity measures to other patient- and treatment-
level variables previously associated with adherence
to LTBI therapy. Results revealed that spatial-level
elasticity measures retained their significant and
positive associations with individual patient behav-
ior after adjusting for other patient and treatment
characteristics, as well as alternative treatment
specifications. Thus, the hypothesis of prevalence
elastic behavior adequately and robustly describes
individual LTBI adherence behavior.
The associations between spatial elasticity of
disease and individual adherence could not be
explained by the correlation between spatial and
individual adherence. All discrete choice models
were re-analyzed by replacing the elasticity variable
with only its numerator (i.e., not normalizing by
disease burden). The results included large and sig-
nificant effects that denoted improved adherence as
spatial-level uptake increased, which was expected.
Re-inserting the complete elasticity variable caused
a relatively precipitous decline in adherence for all
diseases. Thus, living in a zip code with higher pre-
vention uptake is a strong indicator of any one
patient in that zip code being adherent, but not if
September/October 2015
the disease burden relevant to TB re-activation is
also relatively high.
This paper confirms that the prevalence-depen-
dent uptake of prevention in the community is con-
sistent with the individuals living in that
community, even after controlling for individual,
spatial, and treatment characteristics. Let us sup-
pose for a moment that the reverse was found: that
is, community-level uptake of prevention is not
consistent with individuals living in that commu-
nity. What would this tell us? Perhaps, that
(unspecified) individual characteristics are some-
how conflicting with or otherwise shifting our
understanding of the expected demand for preven-
tion, given a supply of disease. In that case, it
would be helpful to further analyze to what degree
individual characteristics distort this alignment
(when it occurs—it does not in this investigation).
This also may be one methodological contribution
for future work, re-invigorating our understanding
of individual factors affecting LTBI adherence.
The utility of this analysis for public health
nurses is the awareness that adherence to LTBI
treatment is associated with spatial disease patterns
that influence re-infection or re-activation risk. In
other words, efforts to improve LTBI adherence
may need to extend beyond the clinical relationship
between provider and patient. The Code of Ethics
for Nurses with Interpretive Statements describes
the nurses’ role in treating the community itself as
the patient, stating “Intra-professional collaboration
within nursing is fundamental to effectively
addressing the health needs of patients and the
public” (American Nurses Association, 2001; Garity,
2005). Appropriate interactions between public
health nurses focusing separately on infectious and
chronic disease control may be needed to effectively
implement specific prevention efforts that target
both set of conditions, a strategy previously
described as “cross-utilisation of health-care work-
ers and multiskilling” (Marais et al., 2013). This is
especially needed among a majority foreign-born
population, where nonmonotonic behavioral
responses to risk may instill additional complexities
in the prevention effort.
As used in the current analysis, incorporation of
Geographic Information Systems is one way to eas-
ily and visually facilitate this interaction (Nykiforuk
& Flaman, 2011). Furthermore, newly created and
readily accessible web-based portals designed to
 Fluegge: Prevalence Elastic Behavior and LTBI Treatment
assist in the diagnosis and treatment of LTBI (Miller
et al., 2014) can be used by public health nurses.
The integration of these tools can inform treatment
options for patients in areas where behavioral
response to disease risk is more inelastic (E ~ 0) or
not substantively reduced by the implementation of
shorter treatment regimens. In the current work,
the association between elasticity and adherence
was not changed when considering alternatively
shorter treatment definitions, though this could still
materialize with regimens shorter than 6 months
(i.e., 4RIF alone). Moreover, it is possible that LTBI
adherence could be improved among patients resid-
ing in locales with more elastic demand (|E| > 1)
merely as a by-product of health messaging target-
ing diabetes and obesity.
Another alternative includes the establishment
of “micro-clinics,” which describes community care
maintained and supported by the community
(Zoughbie, 2009). Such a care model could be
extended from a single-disease focus to a multidis-
ease effort that targets both chronic (diabetes) and
infectious diseases (TB) that correlate significantly
and could also interact to cause a growing disease
burden. If intra-professional collaboration within
the nursing field continues to grow, efforts such as
this could well be realized. The nonmonotonicity in
LTBI prevention behavior among non-English-
speaking patients in the current sample may be
explained, in part, by the increasing prevalence of
these “micro-clinic” models in developing countries
(Demissie, Getahun, & Lindtjørn, 2003; Macq, So-
lis, Martinez, & Martiny, 2008). Thus, this model
may have untapped potential in treating LTBI, a
condition affecting considerably more immigrants.
A number of limitations are present in this
work. First, there remains a significant number of
people with an unconfirmed diabetes diagnosis.
Gregg et al. (2004) found that about 30% of the
total U.S. diabetic population from 1960 to 2000
went undiagnosed, although another found a preva-
lence of undiagnosed diabetes closer to 40% in
2005 (Cowie et al., 2009). More recent analysis has
uncovered improved screening and diagnosis of
diabetes (Selvin, Parrinello, Sacks, & Coresh, 2014).
Nevertheless, poor or no control of an undiagnosed
diabetic condition can increase re-activation likeli-
hood even more than a well-controlled condition.
Leung et al. (2008) noted how diabetics with a
hemoglobin A1c below 7% were not at increased
529
risk of progression to active TB, whereas diabetics
with a hemoglobin A1c above 7% had a relative risk
of more than three. Second, all probit models
excluded an indicator variable of chest X-ray sug-
gestive of previous TB. Although an abnormal chest
radiograph consistent with prior TB is a risk factor
for reactivation (American Thoracic Society, 1999),
the variable, although available, was not used in
this analysis given the uncertainty regarding its
interpretive reliability as a reactivation predictor
(Eisenberg & Pollock, 2010). Finally, this analysis
disregards the potential causative action of myco-
bacteria on diabetes, which has a complex (and
marginalized) history (Broxmeyer, 2005). Such
consideration would have necessitated an instru-
mental variables probit model (Newey, 1987), treat-
ing diabetes prevalence as an endogenous
phenomena.
Although it is impossible to conclude that spa-
tial patterns of disease cause the dropout seen in
this clinic sample, it is important to describe the
communities from which these patients come to
understand how re-activation can happen and what
can be done to mitigate its occurrence. Social eco-
logical models of health suggest multiple levels of
influence on health behavior, including communi-
ties (Glanz & Bishop, 2010). This analysis posits
that researchers and public health practitioners may
need to consider a more comprehensive, hierarchi-
cal explanation of LTBI adherence. Unfortunately,
multilevel modeling was not appropriate for this
data given that spatial disease exposures changed at
the treatment visit level. However, future work may
use multilevel analyses on a subset of this sample.
It may be insufficient to continue treating LTBI
without recognition of the role that behavioral
response to disease risk can play in its re-activation
potential. Health care providers, nurses in particu-
lar, can effectuate advances in this sense by consid-
ering multilevel risk factors for re-activation. These
factors include consideration of both patient- and
community-level indicators of risk to more effec-
tively inform pharmacotherapy options used in
resource-constrained public health clinics.
Acknowledgements
The author acknowledges financial support from the Public Health
Preparedness for Infectious Disease (PHPID) program at Ohio State
University as well as the guidance of Dr. Shu-hua Wang.
530 Public Health Nursing Volume 32 Number 5
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