Tuberculosis Contact Investigations - United States, 2003-2012

Morbidity and Mortality Weekly Report
Weekly / Vol. 64 / Nos. 50 & 51
January 1, 2016
Tuberculosis Contact Investigations United States, 20032012

Kai H. Young, MPH1; Melissa Ehman, MPH2; Randall Reves, MD3; Brandy L. Peterson Maddox, MPH1; Awal Khan, PhD1;
Terence L. Chorba, MD1; John Jereb, MD1
Mycobacterium tuberculosis is transmitted through the air

from an infectious patient (index patient) to other persons
(contacts) who share space. Exposure to M. tuberculosis can
result in tuberculosis (TB) disease or latent TB infection
(LTBI), which has no clinical symptoms or radiologic evidence
of disease. The cycle of transmission can be ended by isolating
and treating patients with TB disease, examining contacts,
and treating LTBI to prevent progression to TB disease. CDC
systematically collects aggregate data on contact investigations
from the 50 states, the District of Columbia (DC), and Puerto
Rico. Data from 20032012 were analyzed for trends in yields
from contact investigations, in terms of numbers of contacts
elicited and examined and the estimated number of TB cases
averted through treatment of LTBI among contacts in 2012.
During 20032012, the number of TB cases decreased, while
the number of contacts listed per index patient with contacts
elicited increased. In 2012, U.S. public health authorities
reported 9,945 cases of TB disease (1) and 105,100 contacts.
Among these contacts, 84,998 (80.9%) were examined; TB
was diagnosed in 532 (0.6%) and LTBI in 15,411 (18.1%).
Among contacts with LTBI, 10,137 (65.8%) started treatment, and 6,689 (43.4% of all contacts with LTBI) completed
treatment. By investigating contacts in 2012, an estimated 128
TB cases (34% of all potential cases) over the initial 5 years
were averted, but an additional 248 cases (66%) might have
been averted if all potentially contagious TB patients had
contacts elicited, all contacts were examined, and all infected
contacts completed treatment. Enhancing contact investigation
activities, particularly by ensuring completion of treatment by
contacts recently infected with M. tuberculosis, is essential to
achieve the goal of TB elimination.
The reporting system for TB contact investigations is
designed to document workload and productivity of state and
local health departments (2). Contact classification and instructions for reporting are described in a users manual and national
guidelines (3,4). Data are collected based on the cascade of

contact investigation activities, from eliciting contacts through
completing treatment for LTBI. The reporting cycle lasts more
than 2 years, reflecting the time required for investigation and
completion of interventions (24). The data, aggregated at the
reporting jurisdiction, are grouped into three categories based
on the expected infectiousness of index patients: 1) sputum
smear-positive pulmonary TB (i.e., presence of acid-fast bacilli
on sputum-smear microscopy), 2) sputum smear-negative,
but culture-positive pulmonary TB, and 3) all other cases and
investigations (e.g., source-case investigations or investigations
conducted to find persons who might have been infected from
the same source as an index case) (3,4). The number and
types of index patients investigated in the third category are
not reported nationally because of jurisdictional variations in
policy and practice (3).
For the period 20032012, data from 44 states and Puerto
Rico were examined for trends; jurisdictions with gaps in
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Centers for Disease Control and Prevention
annual reporting were excluded from this analysis. For 2012,

data from all 50 states, DC, and Puerto Rico were summarized.
To calculate the number of TB cases that were averted by treating LTBI diagnosed during contact investigations in 2012, an
estimated 2.4% (95% confidence interval [CI]=1.2%4.7%)
cumulative 5-year incidence without treatment (5) was used,
discounted for an estimated 80% treatment effectiveness
(based on findings of efficacy in clinical trials) (6). Incomplete
treatment of LTBI was considered equivalent to no treatment. Missed opportunities for prevention were calculated by
projecting the number of missed contacts from patients with
no contact elicited or outcomes at each step of the contact
investigation by the observed proportions. The projections
for completing treatment were discounted by the observed
proportions of patients not completing for reasons of death,
adverse medication effects, health care provider decisions to
discontinue treatment, and development of TB disease.
During 20032012, the 44 states and Puerto Rico reported
114,003 TB cases in surveillance, accounting for 90.2% of all
TB cases reported in the United States and Puerto Rico (1).
During this time, the number of index patients in the 44 states
and Puerto Rico decreased while the number of contacts listed
per index patient with contacts elicited increased from 14.9
to 21.3 contacts for sputum smear-positive index patients
(Table 1). The percentage of index patients with no contact
elicited decreased overall, from 7.2% in 2003 to 5.1% in
2012 for smear-positive patients and from 18.6% to 11.3%
for smear-negative, culture-positive patients. The percentage of contacts who were fully examined remained stable at
approximately 80%. The prevalence rates of both TB disease
and LTBI decreased among contacts of smear-positive and
smear-negative, culture-positive index patients. However, the
yields of TB and LTBI diagnosed among contacts per index
patient with contacts elicited remained stable, with an average of 0.11 contacts with TB disease and 3.13 contacts with
LTBI per smear-positive index patient and 0.05 contacts with
TB disease and 1.30 contacts with LTBI per smear-negative,
culture-positive index patient with contacts elicited. Among
contacts of smear-positive index patients who had a diagnosis
of LTBI, the treatment completion rate remained stable as
well, averaging 46.4% over the 10-year period. The pattern
was similar for contacts of smear-negative, culture-positive
index patients (Table 1).
During 20032012, the reason for not completing treatment was reported for 33,012 (78.8%) of 41,886 contacts
who started, but did not complete treatment for LTBI, from
all three categories of investigations. These reasons are mutually exclusive; if multiple factors were involved, the following
hierarchy was applied: died (201; 0.6%), TB disease developed
(215; 0.7%), adverse effect of treatment (2,263; 6.9%), health
care provider decision (1,859; 5.6%), individual decision
(15,173; 46.0%), moved and outcome was unavailable (3,240;
9.8%), or lost to follow-up (10,061; 30.5%).
The MMWR series of publications is published by the Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention (CDC),
U.S. Department of Health and Human Services, Atlanta, GA 30329-4027.
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MMWR / January 1, 2016 / Vol. 64 / Nos. 50 & 51
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US Department of Health and Human Services/Centers for Disease Control and Prevention
TABLE 1. Results of tuberculosis contact investigations 44 states* and Puerto Rico, 20032012
Patient
classification/
Year
Smear-positive**
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
Smear-negative,
culture-positive
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
Others
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
No. of
patients
No. of
with no
index
contacts
patients for elicited
investigation
(%)
Total
no. of
contacts
elicited
No. of
contacts
examined
(%)
No. of
No. of
contacts
contacts
with
with
TB diagnosis LTBI diagnosis
(%)
(%)
No. with
LTBI who
initiated
treatment
(%)
Yields
No. with
per patient
LTBI who
with contacts elicited
completed
treatment Contacts
TB
LTBI
(%)
elicited diagnoses diagnoses
41,646
4,928
5,020
4,397
4,619
4,312
4,326
3,665
3,532
3,532
3,315
23,549
2,689 (6.5)
355 (7.2)
356 (7.1)
308 (7.0)
353 (7.6)
276 (6.4)
325 (7.5)
202 (5.5)
178 (5.0)
167 (4.7)
169 (5.1)
3,231 (13.7)
692,672
67,919
78,322
63,652
70,103
68,964
75,759
66,112
63,795
70,935
67,111
188,422
569,526 (82.2)
55,031 (81.0)
64,953 (82.9)
52,708 (82.8)
56,483 (80.6)
56,869 (82.5)
62,270 (82.2)
55,314 (83.7)
53,068 (83.2)
57,424 (81.0)
55,406 (82.6)
152,877 (81.1)
4,307 (0.8)
530 (1.0)
491 (0.8)
449 (0.9)
371 (0.7)
414 (0.7)
438 (0.7)
354 (0.6)
485 (0.9)
438 (0.8)
337 (0.6)
915 (0.6)
121,837 (21.4)
14,301 (26.0)
15,396 (23.7)
12,267 (23.3)
12,241 (21.7)
12,861 (22.6)
12,400 (19.9)
10,594 (19.2)
10,495 (19.8)
11,003 (19.2)
10,279 (18.6)
26,424 (17.3)
86,975 (71.4)
10,599 (74.1)
10,851 (70.5)
8,611 (70.2)
8,952 (73.1)
9,039 (70.3)
8,793 (70.9)
7,699 (72.7)
7,702 (73.4)
7,806 (70.9)
6,923 (67.4)
17,846 (67.5)
56,514 (46.4)
6,317 (44.2)
6,669 (43.3)
5,498 (44.8)
5,931 (48.5)
6,201 (48.2)
5,625 (45.4)
5,206 (49.1)
5,257 (50.1)
5,244 (47.7)
4,566 (44.4)
11,745 (44.4)
17.8
14.9
16.8
15.6
16.4
17.1
18.9
19.1
19.0
21.1
21.3
9.3
0.11
0.12
0.11
0.11
0.09
0.10
0.11
0.10
0.14
0.13
0.11
0.05
3.13
3.13
3.30
3.00
2.87
3.19
3.10
3.06
3.13
3.27
3.27
1.30
2,710
2,672
2,390
3,137
3,023
2,261
1,991
1,937
1,810
1,618
505 (18.6)
392 (14.7)
345 (14.4)
362 (11.5)
341 (11.3)
414 (18.3)
271 (13.6)
220 (11.4)
198 (10.9)
183 (11.3)
18,833
21,425
20,613
19,909
18,901
22,082
16,778
17,850
15,666
16,365
163,150
19,941
20,005
18,761
15,839
16,431
16,067
12,210
17,755
14,477
11,664
15,260 (81.0)
16,979 (79.2)
16,523 (80.2)
16,051 (80.6)
15,629 (82.7)
18,037 (81.7)
14,007 (83.5)
14,631 (82.0)
12,717 (81.2)
13,043 (79.7)
135,404 (83.0)
16,914 (84.8)
16,589 (82.9)
16,053 (85.6)
13,199 (83.3)
12,339 (75.1)
13,917 (86.6)
10,349 (84.8)
14,699 (82.8)
11,985 (82.8)
9,360 (80.2)
111 (0.7)
108 (0.6)
93 (0.6)
92 (0.6)
73 (0.5)
103 (0.6)
92 (0.7)
90 (0.6)
83 (0.7)
70 (0.5)
1,013 (0.7)
100 (0.6)
166 (1.0)
89 (0.6)
84 (0.6)
103 (0.8)
85 (0.6)
82 (0.8)
134 (0.9)
107 (0.9)
63 (0.7)
2,959 (19.4)
3,386 (19.9)
2,688 (16.3)
2,933 (18.3)
2,898 (18.5)
2,808 (15.6)
2,135 (15.2)
2,220 (15.2)
2,291 (18.0)
2,106 (16.1)
21,071 (15.6)
2,831 (16.7)
3,052 (18.4)
2,148 (13.4)
1,911 (14.5)
1,894 (15.3)
2,061 (14.8)
1,618 (15.6)
2,018 (13.7)
2,002 (16.7)
1,536 (16.4)
2,203 (74.5)
2,405 (71.0)
1,857 (69.1)
1,998 (68.1)
1,976 (68.2)
1,805 (64.3)
1,505 (70.5)
1,445 (65.1)
1,398 (61.0)
1,254 (59.5)
14,329 (68.0)
2,004 (70.8)
2,123 (69.6)
1,459 (67.9)
1,157 (60.5)
1,345 (71.0)
1,368 (66.4)
1,133 (70.0)
1,445 (71.6)
1,338 (66.8)
957 (62.3)
1,324 (44.7)
1,504 (44.4)
1,225 (45.6)
1,336 (45.6)
1,406 (48.5)
1,169 (41.6)
1,010 (47.3)
990 (44.6)
930 (40.6)
851 (40.4)
9,005 (42.7)
1,212 (42.8)
1,244 (40.8)
908 (42.3)
731 (38.3)
872 (46.0)
809 (39.3)
735 (45.4)
980 (48.6)
902 (45.1)
612 (39.8)
8.5
9.4
10.1
7.2
7.0
12.0
9.8
10.4
9.7
11.4
0.05
0.05
0.05
0.03
0.03
0.06
0.05
0.05
0.05
0.05
1.34
1.49
1.31
1.06
1.08
1.52
1.24
1.29
1.42
1.47
Abbreviations: LTBI = latent TB infection; TB = tuberculosis disease.

* Excludes Georgia, Louisiana, Pennsylvania, Washington, Wisconsin, Wyoming, and the District of Columbia because reports for some years were unobtainable.
As percentages of the numbers in the preceding column.
As percentages of the number of contacts who were examined.
As percentages of the number of contacts with LTBI.
** Smear-positive: pulmonary index patients with acid-fast bacilli reported from sputum-smear microscopy.
Smear-negative, culture-positive: pulmonary index patients without acid-fast bacilli reported from sputum-smear microscopy but with Mycobacterium tuberculosis isolated by culture.
Others: TB patient contact investigations conducted for reasons determined by local policy, such as source-case investigations or investigations conducted to find persons who might
have been infected from the same source as an index patient.
In 2012, health departments in all 50 states, DC, and Puerto

Rico reported 105,100 contacts (Table 2). Contact investigations of sputum smear-positive index patients yielded higher
numbers of contacts elicited (21.2), TB disease diagnoses
(0.11), and LTBI diagnoses (3.26) per index patient with
contacts elicited than did investigations of sputum smearnegative, culture-positive index patients (11.3 contacts elicited,
0.05 TB disease diagnoses, and 1.45 LTBI diagnoses per index
patient with contacts elicited). Among sputum smear-negative,
culture-positive index patients, 12.1% had no contacts elicited,
compared with 5.5% of sputum smear-positive index patients.
The number of contacts with TB disease and LTBI diagnoses
per smear-positive index patient with contacts elicited was more
than twice the number per smear-negative, culture-positive

index patient with contacts elicited.
Based on TB contact investigations in 2012 in all 50
states, DC, and Puerto Rico, a projected estimate of 128
(CI=64252) TB cases were averted over a 5-year span by
treating 6,689 contacts with LTBI (Table 3). An estimated
additional 248 TB cases could have been averted by initiation
and completion of LTBI treatment among missed contacts,
contacts who were not examined, and those who did not start
or complete treatment because the patient moved, was lost to
follow-up, or chose to stop treatment. Overall, contact investigations resulted in the diagnosis of TB in 532 (76%) of 697
contacts projected to have TB disease and averted an estimated
1371
TABLE 2. Results of tuberculosis contact investigations United States* and Puerto Rico, 2012
No. of
patients
No. of
with no
index
contacts
patients for elicited
investigation
(%)
Patient
classification
Smear-positive**
Smear-negative,
culture-positive
Others
Total
3,681
1,840
201 (5.5)
223 (12.1)
Yields
per patient
with contacts elicited
No. with
LTBI who
initiated
treatment
(%)
No. with
LTBI who
completed
treatment
(%)
7,668 (67.6)
1,384 (59.1)
5,052 (44.6)
945 (40.4)
21.2
11.3
0.11
0.05
3.26
1.45
13,265 10,567 (79.7) 69 (0.7)

1,734 (16.4)
1,085 (62.6)
105,100 84,998 (80.9) 532 (0.6) 15,411 (18.1) 10,137 (65.8)
692 (39.9)
6,689 (43.4)
Total
no. of
contacts
elicited
No. of
contacts
examined
(%)
No. of
No. of
contacts contacts with
with TB
LTBI
diagnosis diagnosis
(%)
(%)
73,602 60,120 (81.7) 380 (0.6) 11,337 (18.9)

18,233 14,311 (78.5) 83 (0.6)
2,340 (16.4)
Contacts
TB
LTBI
elicited diagnoses diagnoses
Abbreviations: LTBI = latent TB infection; TB = tuberculosis disease.

* Includes all 50 states and the District of Columbia.
As percentages of the numbers in the preceding column.
As percentages of the number of contacts who were examined.
As percentages of the number of contacts with LTBI.
** Smear-positive: pulmonary index patients with acid-fast bacilli reported from sputum-smear microscopy.
Smear-negative, culture-positive: pulmonary index patients without acid-fast bacilli reported from sputum-smear microscopy but with Mycobacterium tuberculosis isolated by culture.
Others: TB patient contact investigations conducted for reasons determined by local policy, such as source-case investigations or investigations conducted to find persons who might
have been infected from the same source as an index patient.
128 (34%) of the 376 TB cases that could have been averted
in the initial 5-year period, if every possible intervention had
been completed.
Discussion
Although the number of TB cases in 44 states and Puerto

Rico and the percentage of index patients with no contacts
elicited declined from 2003 to 2012, the percentage of contacts who were examined did not change, and fewer than
half of contacts who received a diagnosis of LTBI completed
treatment. In 2012, contacts outnumbered TB cases almost
11 to 1 in the United States, which indicates a burden of public
health work that is not evident from TB case counts alone,
and is thus not apparent to the public or to policy makers.
TB contact investigations are complex interventions, lasting
more than 2 years and requiring specialized skills (4). For
example, after public health authorities assess the contagious
period of an index TB patient, a list of contacts is elicited
by 1) interviewing the index patient or proxies, 2) reviewing
administrative records in congregate settings (e.g., schools),
and 3) visiting sites frequented by the index patient (4). The
procedures required to confirm TB disease or LTBI can take
up to 3 months. The most common regimen for treating LTBI
has been daily isoniazid for 9 months, with monthly health
care visits for monitoring treatment (4).
Because the rate of developing TB disease is highest in the
first 2 years following infection, as are the opportunities for
preventing TB (48), TB contact investigations are efficient
for finding previously undiagnosed cases and detecting newly
acquired LTBI. For the period 20032012, for every smearpositive TB patient with contacts elicited, an average of three
contacts with LTBI were found, and for every 10 smear-positive
TB patients with contacts elicited, one contact had TB disease.
1372
Among all contacts who were examined from 2003 to 2012,

0.7% received a diagnosis of TB disease, a percentage slightly
smaller than the 1%3% reported globally in epidemiologic
studies (7). Since 2012, the World Health Organization has
recommended contact investigations as part of the global TB
control strategy, focusing on the most vulnerable contacts with
the most intense exposure for low-resource settings (8). For
settings with more resources, larger and more intensive contact
investigations are recommended (4,8).
The estimate of 128 potential TB cases averted through
treatment of LTBI in TB contact investigations in 2012 is
conservative. The risk for TB developing without treatment
extends for the lifetime of infected contacts, far beyond this
estimate of cases averted during the first 5 years after infection.
Further, this estimate does not include any projections of cases
averted from secondary transmission or partial effectiveness
of LTBI treatment among patients who started but did not
complete treatment.
The findings in this report are subject to at least three limitations. First, the reports contain no information about whether
all persons who were included as contacts had significant
exposure to the index patient, or whether all persons who
were exposed were included as contacts in the investigations.
Second, the data are not linked to the index TB cases reported
to the National Tuberculosis Surveillance System (1). Finally,
data are not externally validated, and risk stratification (e.g.,
for HIV infection) is not possible nationally because the data
are aggregated before they are sent to CDC. Nonetheless, the
overall U.S. findings are similar to those from studies using a
variety of methods (1,4,6).
Contact investigations in the United States are not achieving
their full potential for preventing TB because of shortfalls at
several junctures. First, contacts were not elicited for one in
TABLE 3. Projected number of tuberculosis cases averted by contact investigations and number of missed opportunities to avert additional
cases United States* and Puerto Rico, 2012
Patient classification
Smear-positive
Results from investigations
Missed opportunities, total
Patients with no contacts elicited
Contacts not examined
Contacts with LTBI, did not initiate
treatment
Contacts with LTBI, initiated treatment,
not completed**
Smear-negative, culture-positive
Patients with no contacts elicited
treatment
not completed**
Others
treatment
not completed**
Total projected outcomes from
investigations and estimated
missed opportunities
Total missed opportunities
Total no.
Reported contacts
counts
elicited
No. of
contacts
examined
No. of
contacts
with TB
diagnosis
No. of
contacts with
LTBI diagnosis
No. with
LTBI who
initiated
treatment
No. with
LTBI who
completed
treatment
Projected no.
TB cases averted
(95% CI)
201
13,482
3,669
73,602
4,261
60,120
4,261
13,482
380
26
81
11,337
805
2,548
7,668
805
2,548
3,669
5,052
770
2,436
3,508
97 (48190)
177 (88346)
15 (729)
47 (2392)
67 (34132)
2,616
2,501
48 (2494)
223
3,922
956
18,233
2,520
14,311
2,520
3,922
83
15
24
2,340
413
643
1,384
413
643
956
945
387
603
897
18 (936)
44 (2285)
7 (415)
12 (623)
17 (934)
439
412
8 (415)
2,698
649
13,265
10,567
2,698
69
19
1,734
442
1,085
442
649
692
418
613
13 (726)
27 (1453)
8 (416)
12 (623)
393
371
7 (414)
111,881
109,361
697
20,262
20,262
19,605
376 (189737)
105,100
6,781
84,998
24,363
532
165
15,411
4,851
10,137
10,125
6,689
12,916
128 (64252)
248 (125486)
Abbreviations: CI = confidence interval; LTBI = latent TB infection; TB = tuberculosis disease.

* Includes all 50 states and the District of Columbia.
Number of TB cases averted = number of contacts with LTBI who completed treatment multiplied by 2.4% (cumulative 5-year incidence without treatment) and
80.0% (estimated treatment effectiveness).
Smear-positive: pulmonary index patients with acid-fast bacilli reported from sputum-smear microscopy.
Missed opportunities for prevention: potential number of contacts elicited = number of patients with no contact elicited multiplied by the number of contacts
elicited per index patient investigated (21.2 for smear-positive, 11.3 for smear-negative, culture-positive index patient investigated); potential number of contacts
examined = number of contacts elicited (assuming all contacts elicited are examined); potential number of contacts with TB diagnosis = number of contacts not
examined multiplied by 0.6% (proportion with TB diagnosis among contacts of smear-positive, or smear-negative, culture-positive patients) or 0.7% (among other
contacts); potential number of contacts with LTBI diagnosis = number of contacts not examined multiplied by 18.9% (proportion with LTBI diagnosis among
contacts of smear-positive patients) or 16.4% (among contacts of smear-negative, culture-positive patients, or other contacts); potential number contacts with
LTBI who initiated treatment = number with LTBI diagnosis (assuming all contacts diagnosed with LTBI initiate treatment) or number with LTBI who did not initiate
treatment; potential number of contacts with LTBI who completed treatment = number with LTBI who initiated treatment, or number of LTBI who initiated treatment,
but did not complete, subtracting the proportion not completing for reasons of death, adverse effects, health care provider decisions to discontinue treatment,
and TB disease developed (4.4% for contacts of smear-positive patients, 6.2% for contacts of smear-negative, culture-positive patients, and 5.5% for other contacts).
** Includes contacts who moved, were lost to follow-up, or decided to stop treatment.
Smear-negative, culture-positive: pulmonary index patients without acid-fast bacilli reported from sputum-smear microscopy but with Mycobacterium tuberculosis
isolated by culture.
Others: TB patient contact investigations conducted for reasons determined by local policy, such as source-case investigations or investigations conducted to find
persons who might have been infected from the same source as an index patient.
Projected outcomes from investigations are the sum of results from investigations and the estimated missed opportunities from each step of the contact
investigation process.
13 potentially infectious (smear-positive or smear-negative,

culture-positive) index patients in 2012. Although contact
elicitation has improved over the years, and success could be
attributed to the guidance encouraging prioritization of activities based on the infectiousness of index patients (4), efforts
should be made to ensure that contacts are elicited from all
potentially infectious patients. Second, one in five contacts

were not examined. Third, more than half of infected contacts
did not complete a regimen for preventing TB. Treatment is
recommended for all contacts who have LTBI (4), but one
third of persons with LTBI did not start treatment, possibly
because of patient or health care provider misperceptions about
1373
Summary
What is already known on this topic?
Tuberculosis (TB) disease is spread person-to-person by the
airborne route. Investigating contacts of contagious TB patients,
a globally recommended strategy, finds new TB cases.
Additional cases can be prevented by treating contacts who
have latent TB infection (LTBI).
What is added by this report?
From 2003 to 2012, the number of TB cases decreased, while
the number of contacts listed per index patient with contacts
elicited increased. For 2012, the United States reported an
average of 11 contacts for every TB case counted (21 contacts
for each of the most contagious TB patients with contacts
elicited). Approximately 1% of contacts already had TB at the
time of examination. An estimated 128 cases over 5 years were
averted by treating LTBI among contacts in 2012. However, an
additional 248 cases could have been prevented if all infectious
TB patients had contacts identified, all contacts received a
medical examination, and contacts with LTBI started and
completed treatment.
What are the implications for public health practice?
TB contact investigations in the United States are productive.
The workload and yield of TB contact investigations are not
reflected in the number of cases that are routinely reported
in TB surveillance. Increasing the number of contacts
with LTBI diagnoses who start and complete treatment
would considerably reduce the number of TB cases in the
United States.
risks and benefits of treatment for LTBI (4,6,8). Furthermore,

one third of all infected contacts who started treatment did
not complete it.
A major barrier to completing treatment has been the
9-month isoniazid regimen. A briefer combination regimen
of isoniazid-rifapentine administered once a week as directly
observed therapy over 12 weeks, which some health departments began to implement in 2012, can increase treatment
initiation and completion rates (9), and innovative case management strategies building on collaborations between health
care systems could minimize loss to follow-up and ensure
1374
treatment completion. Increasing the treatment of LTBI for

multiple risk groups, including contacts recently infected with
M. tuberculosis, is essential for achieving TB elimination (10).
Acknowledgments
State and local TB control officials; Linda Leary; Division of
Tuberculosis Elimination program consultants.
1Division of Tuberculosis Elimination, National Center for HIV/AIDS, Viral
Hepatitis, STD, and TB Prevention, CDC; 2Division of Communicable Disease
Control, Center for Infectious Diseases, California Department of Public
Health; 3Denver Public Health Department.
Corresponding author: Kai H. Young, deq0@cdc.gov, 404-639-2217.
References
1. CDC. Reported tuberculosis in the United States, 2012. Atlanta, GA:
US Department of Health and Human Services, CDC; 2013. Available
at http://www.cdc.gov/tb/statistics/reports/2012/pdf/report2012.pdf.
2. Jereb J, Etkind SC, Joglar OT, Moore M, Taylor Z. Tuberculosis contact
investigations: outcomes in selected areas of the United States, 1999. Int
J Tuberc Lung Dis 2003;7(Suppl 3):S38490.
3. CDC. Aggregate reports for tuberculosis program evaluation: training
manual and users guide. Atlanta, GA: US Department of Health and
Human Services, CDC; 2005. Available at http://www.cdc.gov/tb/
publications/pdf/arpes_manualsm1.pdf.
4. CDC. Guidelines for the investigation of contacts of persons with infectious
tuberculosis; recommendations from the National Tuberculosis Controllers
Association and CDC. MMWR Recomm Rep 2005;54(No. RR-15).
5. Sloot R, Schim van der Loeff MF, Kouw PM, Borgdorff MW. Risk of
tuberculosis after recent exposure. A 10-year follow-up study of contacts
in Amsterdam. Am J Respir Crit Care Med 2014;190:104452.
6. Lobue P, Menzies D. Treatment of latent tuberculosis infection: an
update. Respirology 2010;15:60322.
7. Fox GJ, Barry SE, Britton WJ, Marks GB. Contact investigation
for tuberculosis: a systematic review and meta-analysis. Eur Respir J
2013;41:14056.
8. World Health Organization. Recommendations for investigating
contacts of persons with infectious tuberculosis in low- and
middle-income countries. Geneva, Switzerland: World Health
Organization; 2012. Available at http://apps.who.int/iris/
bitstream/10665/77741/1/9789241504492_eng.pdf?ua=1.
9. CDC. Recommendations for use of an isoniazid-rifapentine regimen with
direct observation to treat latent Mycobacterium tuberculosis infection.
MMWR Morb Mortal Wkly Rep 2011;60:16503.
10. Hill AN, Becerra J, Castro KG. Modelling tuberculosis trends in the
USA. Epidemiol Infect 2012;140:186272.
Fatal Bacterial Meningitis Possibly Associated with Substandard Ceftriaxone

Uganda, 2013
Jason W. Nickerson, PhD1; Amir Attaran, DPhil2; Brian D. Westerberg, MD3; Sharon Curtis, PhD2; Sean Overton2; Paul Mayer, PhD2
The burden of disease from bacterial meningitis is highest

in low-income countries (1). Early initiation of antibiotic
therapy is important in reducing the risk for mortality. Current
treatment guidelines recommend the use of an expandedspectrum cephalosporin (cefotaxime or ceftriaxone) (2), but
these therapies increasingly are limited by drug resistance,
and are threatened by the proliferation of substandard and
falsified medicines (3,4). In February 2013, a case of bacterial
meningitis following a middle ear infection was diagnosed in
an adolescent at the Mulago National Referral Hospital in
Kampala, Uganda. Once-daily treatment with 2 g of intravenous ceftriaxone administered according to guidelines failed,
and the patient died. To determine whether the patients treatment failure and subsequent death might be related to the
ceftriaxone product administered, a sealed vial similar to the
one administered to the patient was analyzed at the University
of Ottawa, Canada, and was found to contain only 0.455 g of
the drug, not 1 g as stated by the manufacturer. This would
have resulted in subtherapeutic dosing. Substandard medicines
are a global problem that disproportionately affects low-income
countries, leading to fatal consequences and promoting the
emergence of drug resistance (4).
On February 7, 2013, a boy aged 13 years from central
Kampala was evaluated at the Mulago National Referral
Hospital in Kampala, Uganda. He had experienced 10 days
of confusion, followed by fevers, chills, rigors, and intermittent vomiting. On otoscopic examination, pus was visible in
the right ear canal, and there was tenderness over the right
mastoid. Neither computed tomography nor lumbar puncture
testing was available at the time of the patients evaluation,
and a presumptive diagnosis of otogenic bacterial meningitis
was made. The patient was admitted to the hospital, and
treatment with 2 g intravenous ceftriaxone once daily was
initiated. Ceftriaxone is recommended as the primary drug for
treatment of meningitis and is available in the public health
system in Uganda (2).
On the fourth treatment day, the patient remained febrile
and lethargic, and 500 mg of intravenous metronidazole given
twice daily was added to the regimen. The following day, the
patient had a worsening headache, and he became irritable and
agitated. Antibiotic therapy was continued, and because of the
failure of medical therapy, a mastoidectomy was planned for
treatment day 7; however, the patient had seizures that day.
Computed tomography, which became available only that

day, demonstrated multiple small abscesses in the posterior
cranial fossa. Neurosurgeons advised that these abscesses were
likely to respond to antibiotics (5), and considering the risks
associated with neurosurgery in a resource-constrained setting,
recommended a conservative approach. Therefore, only the
planned mastoidectomy was performed; no specimens were
sent for culture. Postoperatively, the patient was admitted to
the intensive care unit and started on second-line treatment
with meropenem (1 g three times daily), phenytoin (500 mg
daily), and tramadol (50 mg three times daily). On day 8, when
the patient failed to respond to treatment, levofloxacin and
clindamycin were added. On day 10, the patient experienced
acute respiratory failure, requiring endotracheal intubation
and mechanical ventilation. On day 11, peripheral and corneal
reflexes were absent, and the patient was declared brain dead,
presumably from elevated intracranial pressure. On day 12,
treatment was withdrawn.
Suspecting that the patients initial treatment failure
might be related to the potency of the ceftriaxone product
administered, physicians obtained a sealed vial of injectable
ceftriaxone sodium (labeled 1 g), similar to that administered
to the patient, from the hospital dispensary for testing. The
sample was unexpired and stored according to manufacturers
guidelines. Upon examination of the vial, no obvious signs
of falsification (such as spelling or typographical errors on
the packaging or on the vial) were observed. It was unknown
whether this vial was from the same lot as the one used to
treat the patient.
Analysis of the sample was performed at the John L. Holmes
Mass Spectrometry Facility at the University of Ottawa,
Canada, using established laboratory methods (6). The presence and quantity of active ingredient was verified by mass
spectrometry with an analytical standard of 92% ceftriaxone
disodium salt and a vial of ceftriaxone sodium BP. The sample
contained only 0.455 g of the drug, not 1 g as stated by the
manufacturer and indicated on the label. If the vials administered to the patient were similarly compromised, the patient
would have received a subtherapeutic dose of ceftriaxone,
which might have contributed to treatment failure (7).
1375
Summary
Falsified and substandard medicines, particularly antimalarial
and antiretroviral drugs, are a major threat to global public
health, and have been detected in markets around the world.
The scope of this problem across different drug classes,
including antibiotics, has not been adequately characterized.
A case of fatal bacterial meningitis was possibly associated with
administration of substandard ceftriaxone containing less than
half of the stated active pharmaceutical ingredient.
Substandard or falsified ceftriaxone might be a cause of
treatment failure in bacterial meningitis in Africa.
The presence and use of substandard medicines, particularly
antibiotics, is likely to contribute to treatment failures and
emergence of drug resistance. It is important for public health
practitioners to be aware of both the potential harms and the
large scale of these medicines. National and international
pharmacovigilance is important to prospectively identify poor
quality medicines.
Discussion
Although antibiotic resistance has been documented globally,

and treatment failure can result from multiple factors related to
limitations common in resource-poor environments, including complex or atypical disease progression, ceftriaxone is the
recommended first-line treatment for bacterial meningitis in
Africa (2). Substandard or intentionally adulterated medicinal
products are a global problem that disproportionately affects
low-income countries, where regulation of the pharmaceutical
market is often limited. In addition to leading to treatment
failures, these medicines also contribute to emerging antibiotic resistance in the community, and can erode confidence
in health systems (4). Drugs containing little or no active
ingredient, including first-line therapies for the treatment of
tuberculosis, malaria, and human immunodeficiency virus,
have been found in many low-income countries (4). A recent
meta-analysis of 21 surveys of antimalarial drug quality in
21 sub-Saharan African countries revealed that, of 2,297
samples included, 796 (35%) failed chemical analysis, and
79 of 389 (20%) samples appeared falsified, and thus criminal in origin (8). A study from Pakistan highlighted similar
quality concerns in injectable ceftriaxone, finding that 15.6%
of 96 samples tested were outside acceptable quality ranges
(9). In May 2015, the World Health Organization released a
Medical Product Alert warning of falsified meningitis vaccines
1376
circulating in West Africa.* Substandard medicines can result

from multiple supply chain factors, including manufacturing
or handling problems, deliberate criminal fraud by drug manufacturers, or other criminal practices that exploit regulatory
vulnerabilities in drug markets.
The findings in this report are subject to at least three limitations. First, because of a lack of reliable diagnostic tools (e.g.,
computed tomography, lumbar puncture, or bacterial culture),
the specific pathogen present in this case was not identified,
potentially resulting in the selection of an incorrect antimicrobial therapy. Second, it is not known whether the antibiotic that
was tested came from the same lot that was used to treat this
patient. Finally, because of delayed (10 days into the clinical
course) or inadequate interventions, such as reliance on antibiotics as the sole therapy (e.g., no surgical treatment of the
abscesses), and the possibility that the patients disease could
have progressed beyond a point where single antibiotic therapy
might have been effective, it is not known whether higher quality medicines would have altered the progression of disease in
this case. However, the lack of clinical response to first-line
therapy prompted clinicians to question whether the antibiotic
might have been substandard, and analysis found the sample
to contain less than half of the stated amount of antibiotic.
This case highlights the problem of poor quality medicines
and can alert practitioners in Africa to consider the possibility that substandard or falsified ceftriaxone might be a
cause of treatment failure in bacterial meningitis. Averting a
global public health crisis attributed to low-quality medicines
requires coordinated international and national efforts to
identify and remove these products at all levels of distribution.
Establishment of product standards and robust pharmacovigilance systems, in tandem with stronger criminal legislation,
are important for ensuring that patients have access to quality
medications (10) and for enforcing penalties for those who
intentionally produce or sell substandard or falsified medicines.
* More information available at http://www.who.int/medicines/publications/
drugalerts/VF_MenomuneAlertENversion.pdf?ua=1.
Acknowledgment
Eleanor Reimer, MD, British Columbia Childrens Hospital,
Vancouver, Canada.
1Bruyre Research Institute, Ottawa, Ontario, Canada; 2University of Ottawa,
Ottawa, Ontario, Canada; 3University of British Columbia, Vancouver, British
Columbia, Canada; St. Pauls Rotary Hearing Clinic, Vancouver, British
Columbia, Canada.
Corresponding author: Jason W. Nickerson, Jason.Nickerson@uottawa.ca,
613-562-6262 ext. 2906.
References
1. Edmond K, Clark A, Korczak VS, Sanderson C, Griffiths UK, Rudan I.
Global and regional risk of disabling sequelae from bacterial meningitis: a
systematic review and meta-analysis. Lancet Infect Dis 2010;10:31728.
2. World Health Organization. Managing meningitis epidemics in Africa:
a quick reference guide for health authorities and health-care workers.
Geneva, Switzerland: World Health Organization; 2015. Available at
http://www.ncbi.nlm.nih.gov/books/NBK299454/pdf/Bookshelf_
NBK299454.pdf.
3. Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and
antimicrobial treatment of acute bacterial meningitis. Clin Microbiol
Rev 2010;23:46792.
4. Hajjou M, Krech L, Lane-Barlow C, et al. Monitoring the quality of
medicines: results from Africa, Asia, and South America. Am J Trop Med
Hyg 2015;92(Suppl):6874.
5. Rosenblum ML, Hoff JT, Norman D, Edwards MS, Berg BO.

Nonoperative treatment of brain abscesses in selected high-risk patients.
J Neurosurg 1980;52:21725.
6. Willard H, Merritt L, Dean J, Settle F. Instrumental methods of analysis.
7th ed. Marceline, MO: Wadsworth Publishing Company; 1988.
7. Prasad K, Kumar A, Gupta PK, Singhal T. Third generation
cephalosporins versus conventional antibiotics for treating acute bacterial
meningitis. Cochrane Database Syst Rev 2007;(4):CD001832.
8. Nayyar GM, Breman JG, Newton PN, Herrington J. Poor-quality
antimalarial drugs in southeast Asia and sub-Saharan Africa. Lancet
Infect Dis 2012;12:48896.
9. Obaid A. Quality of ceftriaxone in Pakistan: reality and resonance. Pak
J Pharm Sci 2009;22:2209.
10. Binagwaho A, Bate R, Gasana M, et al. Combatting substandard and
falsified medicines: a view from Rwanda. PLoS Med 2013;10:e1001476.
1377
Increases in Drug and Opioid Overdose Deaths United States, 20002014

Rose A. Rudd, MSPH1; Noah Aleshire, JD1; Jon E. Zibbell, PhD1; R. Matthew Gladden, PhD1
On December 18, this report was posted as an MMWR

Early Release on the MMWR website (http://www.cdc.gov/mmwr).
The United States is experiencing an epidemic of drug
overdose (poisoning) deaths. Since 2000, the rate of deaths
from drug overdoses has increased 137%, including a 200%
increase in the rate of overdose deaths involving opioids (opioid
pain relievers and heroin). CDC analyzed recent multiple
cause-of-death mortality data to examine current trends and
characteristics of drug overdose deaths, including the types of
opioids associated with drug overdose deaths. During 2014, a
total of 47,055 drug overdose deaths occurred in the United
States, representing a 1-year increase of 6.5%, from 13.8 per
100,000 persons in 2013 to 14.7 per 100,000 persons in 2014.
The rate of drug overdose deaths increased significantly for both
sexes, persons aged 2544 years and 55 years, non-Hispanic
whites and non-Hispanic blacks, and in the Northeastern,
Midwestern, and Southern regions of the United States.
Rates of opioid overdose deaths also increased significantly,
from 7.9 per 100,000 in 2013 to 9.0 per 100,000 in 2014,
a 14% increase. Historically, CDC has programmatically
characterized all opioid pain reliever deaths (natural and
semisynthetic opioids, methadone, and other synthetic opioids)
as prescription opioid overdoses (1). Between 2013 and 2014,
the age-adjusted rate of death involving methadone remained
unchanged; however, the age-adjusted rate of death involving
natural and semisynthetic opioid pain relievers, heroin, and
synthetic opioids, other than methadone (e.g., fentanyl)
increased 9%, 26%, and 80%, respectively. The sharp increase
in deaths involving synthetic opioids, other than methadone,
in 2014 coincided with law enforcement reports of increased
availability of illicitly manufactured fentanyl, a synthetic
opioid; however, illicitly manufactured fentanyl cannot be
distinguished from prescription fentanyl in death certificate
data. These findings indicate that the opioid overdose epidemic
is worsening. There is a need for continued action to prevent
opioid abuse, dependence, and death, improve treatment
capacity for opioid use disorders, and reduce the supply of
illicit opioids, particularly heroin and illicit fentanyl.
The National Vital Statistics System multiple cause-of-death
mortality files were used to identify drug overdose deaths.*
Drug overdose deaths were classified using the International
Classification of Disease, Tenth Revision (ICD-10), based
on the ICD-10 underlying cause-of-death codes X4044
(unintentional), X6064 (suicide), X85 (homicide), or Y10

Y14 (undetermined intent) (2). Among the deaths with drug
overdose as the underlying cause, the type of opioid involved
is indicated by the following ICD-10 multiple cause-of-death
codes: opioids (T40.0, T40.1, T40.2, T40.3, T40.4, or
T40.6); natural and semisynthetic opioids (T40.2); methadone
(T40.3); synthetic opioids, other than methadone (T40.4); and
heroin (T40.1). Some deaths involve more than one type of
opioid; these deaths were included in the rates for each category
(e.g., a death involving both a synthetic opioid and heroin
would be included in the rates for synthetic opioid deaths and
in the rates for heroin deaths). Age-adjusted death rates were
calculated by applying age-specific death rates to the 2000 U.S
standard population age distribution (3). Significance testing
was based on the z-test at a significance level of 0.05.
During 2014, 47,055 drug overdose deaths occurred in the
United States. Since 2000, the age-adjusted drug overdose
death rate has more than doubled, from 6.2 per 100,000
persons in 2000 to 14.7 per 100,000 in 2014 (Figure 1). The
overall number and rate of drug overdose deaths increased significantly from 2013 to 2014, with an additional 3,073 deaths
occurring in 2014 (Table), resulting in a 6.5% increase in the
age-adjusted rate. From 2013 to 2014, statistically significant
increases in drug overdose death rates were seen for both
males and females, persons aged 2534 years, 3544 years,
5564 years, and 65 years; non-Hispanic whites and nonHispanic blacks; and residents in the Northeast, Midwest
and South Census Regions (Table). In 2014, the five states
with the highest rates of drug overdose deaths were West
Virginia (35.5 deaths per 100,000), New Mexico (27.3),
New Hampshire (26.2), Kentucky (24.7) and Ohio (24.6).
States with statistically significant increases in the rate of
drug overdose deaths from 2013 to 2014 included Alabama,
Georgia, Illinois, Indiana, Maine, Maryland, Massachusetts,
Michigan, New Hampshire, New Mexico, North Dakota,
Ohio, Pennsylvania, and Virginia.
In 2014, 61% (28,647, data not shown) of drug overdose
deaths involved some type of opioid, including heroin. The
age-adjusted rate of drug overdose deaths involving opioids
increased significantly from 2000 to 2014, increasing 14%
from 2013 (7.9 per 100,000) to 2014 (9.0) (Figure 1). From
2013 to 2014, the largest increase in the rate of drug overdose
deaths involved synthetic opioids, other than methadone
* Additional information available at http://www.cdc.gov/nchs/nvss/mortality_

public_use_data.htm.
Additional
1378
information available at http://www.cdc.gov/drugoverdose/data/

statedeaths.html.
FIGURE 1. Age-adjusted rate* of drug overdose deaths and drug

overdose deaths involving opioids, United States, 20002014
10
All drug overdose deaths

Drug overdose deaths involving opioids
14
Deaths per 100,000 population
Deaths per 100,000 population
16
FIGURE 2. Drug overdose deaths* involving opioids,, by type of

opioid United States, 20002014
12
10
8
6
4
2
8
7
6
5
4
3
2
1
0
0
2000
2002
2004
2006
2008
2010
2012
2014
(e.g., fentanyl and tramadol), which nearly doubled from

1.0 per 100,000 to 1.8 per 100,000 (Figure 2). Heroin overdose death rates increased by 26% from 2013 to 2014 and
have more than tripled since 2010, from 1.0 per 100,000 in
2010 to 3.4 per 100,000 in 2014 (Figure 2). In 2014, the rate
of drug overdose deaths involving natural and semisynthetic
opioids (e.g., morphine, oxycodone, and hydrocodone),
3.8 per 100,000, was the highest among opioid overdose
deaths, and increased 9% from 3.5 per 100,000 in 2013. The
rate of drug overdose deaths involving methadone, a synthetic
opioid classified separately from other synthetic opioids, was
similar in 2013 and 2014.
Discussion
More persons died from drug overdoses in the United States

in 2014 than during any previous year on record. From 2000
to 2014 nearly half a million persons in the United States have
died from drug overdoses. In 2014, there were approximately
one and a half times more drug overdose deaths in the United
States than deaths from motor vehicle crashes (4). Opioids,
primarily prescription pain relievers and heroin, are the main
drugs associated with overdose deaths. In 2014, opioids were
involved in 28,647 deaths, or 61% of all drug overdose deaths;
the rate of opioid overdoses has tripled since 2000. The 2014
data demonstrate that the United States opioid overdose
2000
2002
2004
2006
2008
2010
2012
2014
Year
Year
Source: National Vital Statistics System, Mortality file.
* Age-adjusted death rates were calculated by applying age-specific death rates
to the 2000 U.S. standard population age distribution.
Drug overdose deaths are identified using International Classification of
Diseases, Tenth Revision underlying cause-of-death codes X40X44, X60X64,
X85, and Y10Y14.
Drug overdose deaths involving opioids are drug overdose deaths with a
multiple cause-of-death code of T40.0, T40.1, T40.2, T40.3, T40.4, or T40.6.
Approximately one fifth of drug overdose deaths lack information on the
specific drugs involved. Some of these deaths might involve opioids.
Opioids include drugs such as morphine, oxycodone, hydrocodone, heroin,
methadone, fentanyl, and tramadol.
Drug overdose deaths involving opioids

Natural and semisynthetic opioids
Synthetic opioids excluding methadone
Methadone
Heroin

* Age-adjusted death rates were calculated by applying age-specific death rates
to the 2000 U.S. standard population age distribution.
Drug overdose deaths involving opioids are identified using International
Classification of Diseases, Tenth Revision underlying cause-of-death codes
X40X44, X60X64, X85, and Y10Y14 with a multiple cause code of T40.0,
T40.1, T40.2, T40.3, T40.4, or T40.6.
Opioids include drugs such as morphine, oxycodone, hydrocodone, heroin,
methadone, fentanyl, and tramadol.
For each type of opioid, the multiple cause-of-death code was T40.1 for heroin,
T40.2 for natural and semisynthetic opioids (e.g., oxycodone and hydrocodone),
T40.3 for methadone, and T40.4 for synthetic opioids excluding methadone
(e.g., fentanyl and tramadol). Deaths might involve more than one drug thus
categories are not exclusive.
epidemic includes two distinct but interrelated trends: a

15-year increase in overdose deaths involving prescription
opioid pain relievers and a recent surge in illicit opioid overdose
deaths, driven largely by heroin.
Natural and semisynthetic opioids, which include the most
commonly prescribed opioid pain relievers, oxycodone and
hydrocodone, continue to be involved in more overdose deaths
than any other opioid type. Although this category of opioid
drug overdose death had declined in 2012 compared with 2011,
and had held steady in 2013, there was a 9% increase in 2014.
Drug overdose deaths involving heroin continued to climb
sharply, with heroin overdoses more than tripling in 4 years.
This increase mirrors large increases in heroin use across the
country (5) and has been shown to be closely tied to opioid pain
reliever misuse and dependence. Past misuse of prescription
opioids is the strongest risk factor for heroin initiation and use,
specifically among persons who report past-year dependence
or abuse (5). The increased availability of heroin, combined
with its relatively low price (compared with diverted prescription opioids) and high purity appear to be major drivers of the
upward trend in heroin use and overdose (6).
The rate of drug overdose deaths involving synthetic opioids
nearly doubled between 2013 and 2014. This category
includes both prescription synthetic opioids (e.g., fentanyl
1379
TABLE. Number and age-adjusted rates of drug overdose deaths,* by sex, age, race and Hispanic origin, Census region, and state
United States, 2013 and 2014
2013
Decedent characteristic
All
Sex
Male
Female
Age group (yrs)
014
1524
2534
3544
4554
5564
65
Race and Hispanic origin
White, non-Hispanic
Black, non-Hispanic
Hispanic
Census region of residence
Northeast
Midwest
South
West
State of residence
Alabama
Alaska
Arizona
Arkansas
California
Colorado
Connecticut
Delaware
District of Columbia
Florida
Georgia
Hawaii
Idaho
Illinois
Indiana
Iowa
Kansas
Kentucky
Louisiana
Maine
Maryland
Massachusetts
Michigan
Minnesota
Mississippi
Missouri
Montana
Nebraska
Nevada
New Hampshire
New Jersey
New Mexico
New York
North Carolina
North Dakota
Ohio
Oklahoma
Oregon
See table footnotes on the next page.
1380
No.
2014
Age-adjusted rate
No.
Age-adjusted rate
% change from
2013 to 2014
43,982
13.8
47,055
14.7
6.5
26,799
17,183
17.0
10.6
28,812
18,243
18.3
11.1
7.6
4.7
105
3,664
8,947
9,320
12,045
7,551
2,344
0.2
8.3
20.9
23.0
27.5
19.2
5.2
109
3,798
10,055
10,134
12,263
8,122
2,568
0.2
8.6
23.1
25.0
28.2
20.3
5.6
0.0
3.6
10.5
8.7
2.5
5.7
7.7
35,581
3,928
3,345
17.6
9.7
6.7
37,945
4,323
3,504
19.0
10.5
6.7
8.0
8.2
0.0
8,403
9,745
15,519
10,315
14.8
14.6
13.1
13.6
9,077
10,647
16,777
10,554
16.1
16.0
14.0
13.7
8.8
9.6
6.9
0.7
598
105
1,222
319
4,452
846
582
166
102
2,474
1,098
158
207
1,579
1,064
275
331
1,019
809
174
892
1,081
1,553
523
316
1,025
137
117
614
203
1,294
458
2,309
1,259
20
2,347
790
455
12.7
14.4
18.7
11.1
11.1
15.5
16.0
18.7
15.0
12.6
10.8
11.0
13.4
12.1
16.6
9.3
12.0
23.7
17.8
13.2
14.6
16.0
15.9
9.6
10.8
17.5
14.5
6.5
21.1
15.1
14.5
22.6
11.3
12.9
2.8
20.8
20.6
11.3
723
124
1,211
356
4,521
899
623
189
96
2,634
1,206
157
212
1,705
1,172
264
332
1,077
777
216
1,070
1,289
1,762
517
336
1,067
125
125
545
334
1,253
547
2,300
1,358
43
2,744
777
522
15.2
16.8
18.2
12.6
11.1
16.3
17.6
20.9
14.2
13.2
11.9
10.9
13.7
13.1
18.2
8.8
11.7
24.7
16.9
16.8
17.4
19.0
18.0
9.6
11.6
18.2
12.4
7.2
18.4
26.2
14.0
27.3
11.3
13.8
6.3
24.6
20.3
12.8
19.7
16.7
-2.7
13.5
0.0
5.2
10.0
11.8
-5.3
4.8
10.2
-0.9
2.2
8.3
9.6
-5.4
-2.5
4.2
-5.1
27.3
19.2
18.8
13.2
0.0
7.4
4.0
-14.5
10.8
-12.8
73.5
-3.4
20.8
0.0
7.0
125.0
18.3
-1.5
13.3
TABLE. (Continued) Number and age-adjusted rates of drug overdose deaths,* by sex, age, race and Hispanic origin, Census region, and
state United States, 2013 and 2014
2013
Decedent characteristic
Pennsylvania
Rhode Island
South Carolina
South Dakota
Tennessee
Texas
Utah
Vermont
Virginia
Washington
West Virginia
Wisconsin
Wyoming
No.
2,426
241
620
55
1,187
2,446
594
93
854
969
570
856
98
2014
Age-adjusted rate
19.4
22.4
13.0
6.9
18.1
9.3
22.1
15.1
10.2
13.4
32.2
15.0
17.2
No.
2,732
247
701
63
1,269
2,601
603
83
980
979
627
853
109
Age-adjusted rate
% change from
2013 to 2014
21.9
23.4
14.4
7.8
19.5
9.7
22.4
13.9
11.7
13.3
35.5
15.1
19.4
12.9
4.5
10.8
13.0
7.7
4.3
1.4
-7.9
14.7
-0.7
10.2
0.7
12.8

* Deaths are classified using the International Classification of Diseases, Tenth Revision (ICD10). Drug overdose deaths are identified using underlying cause-of-death
codes X40X44, X60X64, X85, and Y10Y14. Age-adjusted death rates were calculated by applying age-specific death rates to the 2000 U.S standard population
age distribution.
Data for Hispanic origin should be interpreted with caution; studies comparing Hispanic origin on death certificates and on census surveys have shown inconsistent
reporting on Hispanic ethnicity.
Statistically significant change from 2013 to 2014.
and tramadol) and non-pharmaceutical fentanyl manufactured

in illegal laboratories (illicit fentanyl). Toxicology tests used
by coroners and medical examiners are unable to distinguish
between prescription and illicit fentanyl. Based on reports
from states and drug seizure data, however, a substantial portion of the increase in synthetic opioid deaths appears to be
related to increased availability of illicit fentanyl (7), although
this cannot be confirmed with mortality data. For example,
five jurisdictions (Florida, Maryland, Maine, Ohio, and
Philadelphia, Pennsylvania) that reported sharp increases in
illicit fentanyl seizures, and screened persons who died from
a suspected drug overdose for fentanyl, detected similarly
sharp increases in fentanyl-related deaths (7). Finally, illicit
fentanyl is often combined with heroin or sold as heroin. Illicit
fentanyl might be contributing to recent increases in drug
overdose deaths involving heroin. Therefore, increases in illicit
fentanyl-associated deaths might represent an emerging and
troubling feature of the rise in illicit opioid overdoses that has
been driven by heroin.
The findings in this report are subject to at least three limitations. First, several factors related to death investigation might
affect estimates of death rates involving specific drugs. At
autopsy, toxicological laboratory tests might be performed to
determine the type of drugs present; however, the substances
tested for and circumstances under which the tests are performed
vary by jurisdiction. Second, in 2013 and 2014, 22% and 19%
of drug overdose deaths, respectively, did not include information on the death certificate about the specific types of drugs
Additional information available at http://pub.lucidpress.com/NDEWSFentanyl/.
involved. The percent of overdose deaths with specific drugs

identified on the death certificate varies widely by state. Some
of these deaths might have involved opioids. This increase in
the reporting of specific drugs in 2014 might have contributed
to some of the observed increases in drug overdose death rates
involving different types of opioids from 2013 to 2014. Finally,
some heroin deaths might be misclassified as morphine because
morphine and heroin are metabolized similarly (8), which might
result in an underreporting of heroin overdose deaths.
To reverse the epidemic of opioid drug overdose deaths
and prevent opioid-related morbidity, efforts to improve safer
prescribing of prescription opioids must be intensified. Opioid
pain reliever prescribing has quadrupled since 1999 and has
increased in parallel with overdoses involving the most commonly used opioid pain relievers (1). CDC has developed a
draft guideline for the prescribing of opioids for chronic pain
to address this need.
In addition, efforts are needed to protect persons already
dependent on opioids from overdose and other harms. This
includes expanding access to and use of naloxone (a safe
and effective antidote for all opioid-related overdoses)**
and increasing access to medication-assisted treatment, in
combination with behavioral therapies (9). Efforts to ensure
access to integrated prevention services, including access to
syringe service programs when available, is also an important
Additional information available at http://www.cdc.gov/drugoverdose/
prescribing/guideline.html.
** Additional information available at https://store.samhsa.gov/shin/content/
SMA13-4742/Overdose_Toolkit_2014_Jan.pdf.
1381
Summary
The rate for drug overdose deaths has increased approximately
140% since 2000, driven largely by opioid overdose deaths.
After increasing since the 1990s, deaths involving the most
commonly prescribed opioid pain relievers (i.e., natural and
semisynthetic opioids) declined slightly in 2012 and remained
steady in 2013, showing some signs of progress. Heroin
overdose deaths have been sharply increasing since 2010.
Drug overdose deaths increased significantly from 2013 to
2014. Increases in opioid overdose deaths were the main factor
in the increase in drug overdose deaths. The death rate from the
most commonly prescribed opioid pain relievers (natural and
semisynthetic opioids) increased 9%, the death rate from heroin
increased 26%, and the death rate from synthetic opioids, a
category that includes illicitly manufactured fentanyl and
synthetic opioid pain relievers other than methadone, increased
80%. Nearly every aspect of the opioid overdose death
epidemic worsened in 2014.
Efforts to encourage safer prescribing of opioid pain relievers
should be strengthened. Other key prevention strategies
include expanding availability and access to naloxone (an
antidote for all opioid-related overdoses), increasing access to
medication-assisted treatment in combination with behavioral
therapies, and increasing access to syringe service programs to
prevent the spread of hepatitis C virus infection and human
immunodeficiency virus infections. Public health agencies,
medical examiners and coroners, and law enforcement agencies
can work collaboratively to improve detection of and response to
outbreaks associated with drug overdoses related to illicit opioids.
consideration to prevent the spread of hepatitis C virus and

human immunodeficiency virus infections from injection
drug use.
Public health agencies, medical examiners and coroners, and
law enforcement agencies can work collaboratively to improve
1382
detection of outbreaks of drug overdose deaths involving

illicit opioids (including heroin and illicit fentanyl) through
improved investigation and testing as well as reporting and
monitoring of specific drugs, and facilitate a rapid and effective response that can address this emerging threat to public
health and safety (7). Efforts are needed to distinguish the
drugs contributing to overdoses to better understand this trend.
1Division of Unintentional Injury Prevention, National Center for Injury
Prevention and Control, CDC.
Corresponding author: Rose A. Rudd, rvr2@cdc.gov, 770-488-3712.
References
1. Paulozzi LJ, Jones C, Mack K, Rudd R. Vital signs: overdoses of
prescription opioid pain relieversUnited States, 19992008. MMWR
Morb Mortal Wkly Rep 2011;60:148792.
2. Bergen G, Chen LH, Warner M, Fingerhut LA. Injury in the United States:
2007 chartbook. Hyattsville, MD: National Center for Health Statistics;
2008 Available at http://www.cdc.gov/nchs/data/misc/injury2007.pdf.
3. Murphy SL, Xu JQ, Kochanek KD. Deaths: final data for 2010. National vital
statistics reports. Hyattsville, MD: National Center for Health Statistics; 2013.
Available at http://www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_04.pdf.
4. CDC. Wide-ranging online data for epidemiologic research (WONDER).
Atlanta, GA: CDC, National Center for Health Statistics; 2015. Available
at http://wonder.cdc.gov.
5. Jones CM, Logan J, Gladden RM, Bohm MK. Vital signs: demographic
and substance use trends among heroin usersUnited States, 20022013.
MMWR Morb Mortal Wkly Rep 2015;64:71925.
6. Cicero TJ, Ellis MS, Surratt HL, Kurtz SP. The changing face of heroin
use in the United States: a retrospective analysis of the past fifty years.
JAMA Psychiatry 2014;71:8216.
7. CDC. Increases in fentanyl drug confiscations and fentanyl-related
overdose fatalities. HAN Health Advisory. Atlanta, GA: US Department of
Health and Human Services, CDC; 2015. Available at http://emergency.
cdc.gov/han/han00384.asp.
8. Davis GG. Complete republication: National Association of Medical Examiners
position paper: recommendations for the investigation, diagnosis, and
certification of deaths related to opioid drugs. J Med Toxicol 2014;10:1006.
9. Volkow ND, Frieden TR, Hyde PS, Cha SS. Medication-assisted
therapiestackling the opioid-overdose epidemic. N Engl J Med
2014;370:20636.
Notes from the Field

Group A Streptococcal Pharyngitis Misdiagnoses at
a Rural Urgent-Care Clinic Wyoming, March 2015
Alexia Harrist, MD, PhD1,2; Clayton Van Houten, MS2; Stanford T.
Shulman, MD3; Chris Van Beneden, MD4; Tracy Murphy, MD2
Group A Streptococcus (GAS) is the most common bacterial

cause of pharyngitis, implicated in 20%30% of pediatric
and 5%15% of adult health care visits for sore throat (1).
Along with the sudden onset of throat pain, GAS pharyngitis
symptoms include fever, headache, and bilateral tender cervical lymphadenopathy (1,2). Accurate diagnosis and management of GAS pharyngitis is critical for limiting antibiotic
overuse and preventing rheumatic fever (2), but distinguishing
between GAS and viral pharyngitis clinically is challenging (1).
Guidelines for diagnosis and management of GAS pharyngitis have been published by the Infectious Diseases Society of
America (IDSA)* (1). IDSA recommends that patients with
sore throat be tested for GAS to distinguish between GAS
and viral pharyngitis; however, IDSA emphasizes the use of
selective testing based on clinical symptoms and signs to avoid
identifying GAS carriers rather than acute GAS infections (1).
Therefore, testing for GAS usually is not recommended for
the following: patients with sore throat and accompanying
symptoms (e.g., cough, rhinorrhea) that strongly suggest a
viral etiology; children aged <3 years, because acute rheumatic
fever is extremely rare in this age group; and asymptomatic
household contacts of patients with GAS pharyngitis (1). IDSA
recommends penicillin or amoxicillin as the treatment of choice
based on effectiveness and narrow spectrum of activity. To
date, penicillin-resistant GAS has never been documented (1).
In March 2015, a rural urgent-care clinic serving a population of 5,0007,000 reported a substantial increase in GAS
pharyngitis infections since November 2014, with some
infections nonresponsive to penicillin and amoxicillin to the
Wyoming Department of Health (WDH). By March 2015, the
clinic reported diagnosing up to 90 cases of GAS pharyngitis
per week. WDH started an investigation to verify this potential
GAS pharyngitis outbreak, assess clinic testing and treatment
practices, and implement control measures.
WDH reviewed a clinic-provided line list of 42 patients
tested for GAS pharyngitis using rapid antigen detection tests
(RADTs) during March 1317 and two additional patients
who had received diagnoses of GAS pharyngitis the previous
week and returned with persistent symptoms. Patient characteristics stratified by age are provided (Table).
* Available at http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_
Care/PDF_Library/2012%20Strep%20Guideline.pdf.
The line list revealed nonadherence to IDSA guidelines in

testing and treatment procedures. Ten of 34 (29%) patients
aged 3 years who were tested for GAS reported no sore
throat, the symptom that should prompt evaluation for GAS
pharyngitis in patients aged 3 years (1). Two of these 10 were
asymptomatic adult contacts of patients with diagnosed GAS
pharyngitis; both asymptomatic contacts had positive RADT
results and were prescribed an antibiotic. Of the 24 tested
patients aged 3 years with sore throat, 19 (79%) reported
cough or rhinorrhea, symptoms that suggest a viral rather than
bacterial etiology (1). Although diagnostic testing of patients
aged <3 years is not routinely recommended, testing of symptomatic children who are household contacts of persons with
laboratory-confirmed GAS pharyngitis can be considered (1).
Among the seven patients aged <3 years who were tested for
GAS pharyngitis, five (71%) had GAS-positive family members
indicated by shared surname included in the line list; however,
all seven (100%) had cough, and five (71%) had rhinorrhea.
Four of six patients with negative RADT results received an
antibiotic. The clinic practice was to send throat swabs from
patients with negative RADTs to a commercial laboratory for
back-up culture, but it is unknown whether the clinic obtained
any GAS-positive throat cultures from RADT-negative patients.
All patients who were administered an antibiotic received a
cephalosporin, clindamycin, or amoxicillin-clavulanate rather
than penicillin or amoxicillin as the initial antibiotic therapy.
Three patients were prescribed a second course of an antibiotic
because of symptoms persisting >48 hours after the start of
initial therapy; data provided did not indicate whether they
were retested for GAS.
Because of the high positivity rate (38 of 44; 86%) among
RADTs performed, including eight of 10 positive test results
among patients aged 3 years without sore throat, WDH
requested that the clinic perform oropharyngeal cultures on
patients with positive RADTs. The clinic reported that four
throat cultures collected from RADT-positive patients simultaneously with the RADT throat swab had no GAS isolated;
the number of cultures submitted is unknown. Based on these
results, WDH recommended that the clinic review testing
procedures with the RADT manufacturer. The clinic subsequently reported to WDH that staff members were interpreting
certain RADT results later than the recommended maximum
incubation time of 5 minutes, a practice that can result in
false-positives, according to the manufacturer.
WDH and CDC investigators reviewed IDSA guidelines
for diagnosis and management of GAS pharyngitis with
clinic practitioners. GAS cultured from throat swabs during
1383
TABLE. Clinical characteristics of 44 patients evaluated for group A streptococcal pharyngitis (GAS) using a rapid antigen detection test (RADT)
at a rural urgent-care clinic Wyoming, March 2015
Patients aged 3 yrs
(n = 34)
Characteristic
Age group (yrs)
<3
319
2061
Unknown
Symptom
Sore throat
Cough
Rhinorrhea
Fever
Sinus congestion
Nausea
Ear pain
Headache
Fatigue
Vomiting
Lymphadenopathy
Rash
None (GAS exposure only)
Positive RADT result
Initial antibiotic therapy*
1st gen. cephalosporin
2nd gen. cephalosporin
Amoxicillin-clavulanate
Clindamycin
None
Second antibiotic therapy
2nd gen. cephalosporin
Amoxicillin-clavulanate
None
All patients
(N = 44)
No. (%)
Patients aged <3 yrs

(n = 7)
No. (%)
Patients aged 3 yrs

(n = 34)
No. (%)
With sore throat

(n = 24)
No. (%)
With no sore throat

(n = 10)
No. (%)
7 (16)
18 (41)
16 (36)
3 (7)
7 (100)
18 (53)
16 (47)
14 (58)
10 (42)
4 (40)
6 (60)
28 (64)
23 (52)
19 (43)
15 (34)
14 (32)
12 (27)
10 (23)
9 (20)
9 (20)
5 (11)
4 (9)
0
2 (5)
38 (86)
2 (29)
7 (100)
5 (71)
4 (57)
3 (43)
0
1 (14)
0
2 (29)
1 (14)
1 (14)
0
0
6 (86)
24 (71)
15 (44)
13 (38)
9 (26)
11 (32)
11 (32)
9 (26)
9 (26)
6 (18)
4 (12)
3 (9)
0
2 (6)
29 (85)
24 (100)
13 (54)
11 (46)
6 (25)
9 (38)
7 (29)
8 (33)
8 (33)
4 (17)
3 (13)
2 (8)
0
0
21 (88)
0 (0)
2 (20)
2 (20)
3 (30)
2 (20)
4 (40)
1 (10)
1 (10)
2 (20)
1 (10)
1 (10)
0
2 (20)
8 (80)
6 (14)
20 (45)
13 (30)
3 (7)
2 (5)
0 (0)
5 (71)
1 (14)
1 (14)
0
6 (18)
14 (41)
11 (32)
1 (3)
2 (6)
4 (17)
9 (38)
10 (42)
1 (4)
0
2 (20)
5 (50)
1 (10)
0
2 (20)
1 (2)
2 (5)
41 (93)
0
0
7 (100)
1 (3)
2 (6)
31 (91)
1 (4)
2 (8)
21 (88)
0
0
10 (100)
Abbreviations: 1st gen. = first generation; 2nd gen. = second generation.

* Four patients with negative RADT results were prescribed antibiotics.
Data are from March 1317, 2015, only; it is unknown how many patients were prescribed a second antibiotic after March 17.
subsequent weeks was confirmed to be uniformly sensitive

to penicillin and amoxicillin. Subsequently, the number of
RADT-positive GAS pharyngitis cases declined, and the clinic
returned to using penicillin or amoxicillin as first-line therapy.
Based on the available information, investigators determined
that the clinic performed RADTs on patients unlikely to have
GAS pharyngitis (e.g., no sore throat, or sore throat coincident
with cough or rhinorrhea), which is inconsistent with IDSA
guidelines. Possible reasons for RADT-positive results among
these patients are GAS carriage (1) or RADT incubation
periods exceeding manufacturer recommendations. Although
RADTs are highly specific (3) and allow clinicians to make
treatment decisions at the time of the patient visit, incorrect
technique at the point of care can result in false-positives. As
a result of these errors, patients likely to have viral illness were
treated with antibiotics. The patients failure to improve led to
the assumption of bacterial resistance, which prompted use of
1384
broad-spectrum antibiotics as first-line therapy in subsequent

patients. The clinic practitioners recognition of their unusually
high GAS incidence, request for assistance, and compliance
with suggested interventions were critical in identifying and
amending problematic practices.
Sore throat is one of the most common symptoms reported
by outpatients (4,5), with viral infections responsible for the
majority of cases (1). Correct diagnosis and treatment of GAS
pharyngitis prevents acute rheumatic fever, shortens illness
duration, and reduces person-to-person spread (2); however,
antibiotic overuse for sore throat is common among both
children and adults (4,5). This can result in unnecessary side
effects and promote development of antibiotic resistance.
Clinics should take steps to ensure practitioner understanding
of and adherence to published guidelines, and to promote the
use of good laboratory practices, such as periodic evaluation
of competency in testing procedures (6).
1Epidemic Intelligence Service, CDC; 2Public Health Sciences Section,

Wyoming Department of Health; 3 Division of Infectious Diseases,
Ann & Robert H. Lurie Childrens Hospital, Northwestern University School
of Medicine, Chicago, Illinois; 4Division of Bacterial Diseases, National Center
for Immunization and Respiratory Diseases, CDC.
Corresponding author: Alexia Harrist, alexia.harrist@wyo.gov, 307-777-5532.
References
1. Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for
the diagnosis and management of group A streptococcal pharyngitis:
2012 update by the Infectious Diseases Society of America. Clin Infect
Dis 2012;55:127982.
2. Wessels MR. Clinical practice. Streptococcal pharyngitis. N Engl J Med
2011;364:64855.
3. Lean WL, Arnup S, Danchin M, Steer AC. Rapid diagnostic tests

for group A streptococcal pharyngitis: a meta-analysis. Pediatrics
2014;134:77181.
4. Dooling KL, Shapiro DJ, Van Beneden C, Hersh AL, Hicks LA.
Overprescribing and inappropriate antibiotic selection for children
with pharyngitis in the United States, 19972010. JAMA Pediatr
2014;168:10734.
5. Barnett ML, Linder JA. Antibiotic prescribing to adults with sore throat
in the United States, 19972010. JAMA Intern Med 2014;174:13840.
6. Howerton D, Anderson N, Bosse D, Granade S, Westbrook G. Good
laboratory practices for waived testing sites: survey findings from
testing sites holding a certificate of waiver under the clinical laboratory
improvement amendments of 1988 and recommendations for promoting
quality testing. MMWR Recomm Rep 2005;54(No. RR-13).
1385
Notes from the Field

Hepatitis C Outbreak in a Dialysis Clinic
Tennessee, 2014
Daniel Muleta, MD1; Marion A. Kainer, MBBS1; Loretta MooreMoravian1; Andrew Wiese MPH1; Jennifer Ward MSc1; Sheila
McMaster, MSN2; Duc Nguyen, MD3; Joseph C. Forbi, PhD4;
Tonya Mixson-Hayden, PhD4; Melissa Collier, MD4
Outbreaks of hepatitis C virus (HCV) infections can occur

among hemodialysis patients when recommended infection
control practices are not followed (1). On January 30, 2014,
a dialysis clinic in Tennessee identified acute HCV in a patient
(patient A) during routine screening and reported it to the
Tennessee Department of Health. Patient A had enrolled in
the dialysis clinic in March 2010 and had annually tested negative for HCV (including a last HCV test on December 19,
2012), until testing positive for HCV antibodies (anti-HCV)
on December 18, 2013 (confirmed by a positive HCV nucleic
acid amplification test). Patient A reported no behavioral risk
factors, but did have multiple health care exposures.
On April 16, 2014, the Tennessee Department of Health
observed infection control practices at the clinic. Clinic officials reported that no changes to infection control protocols
at the dialysis clinic had been made from the time patient A
was identified to this date of observation. The health department observers noted that no visible blood was present on any
surfaces, sinks were easily accessible, staff hand hygiene was
performed consistently, and gloves and other personal protective equipment were used appropriately. Individual patient stations were disinfected after the previous patient left the station,
with a 1:100 diluted household bleach solution, and surfaces
were allowed to dry completely between patients. Medications
were prepared for each patient in a separate, clean medication
room at the time of administration; no multidose medication
vials were carried into patient care areas. Blood for glucose
testing was drawn from dialysis access sites with a syringe and
tested by a glucometer in the laboratory. The glucometer was
adequately disinfected between uses. Monthly trainings in
infection control had been consistently provided to all staff
members before the outbreak was identified.
Sixty-two dialysis patients were being treated at the clinic at
the time of the investigation; all were retested for HCV. Nine
(15%) patients, including patient A, were HCV-infected;
specimens from patient A and five other chronically infected
dialysis patients were positive for HCV genotype 1a (Figure),
the remaining three were positive for genotype 1b. Genotype 1a
is the most prevalent genotype in the United States (2). Patient
1386
B, who seroconverted in December 2010, had a history of

injection drug use, which, at the time of diagnosis, was considered to be the source of exposure. Patient C was chronically
infected and had tested positive for HCV upon admission
at the dialysis clinic. Infection duration for all other HCV
infected patients, including patient C, was unknown.
Quasispecies (HCV intra-genotype variants) analysis was
performed from serum specimens collected from all nine
patients found to be HCV positive. Patients A, B, and C were
infected with genotype 1a; less than 5% nucleotide variation among intra-host HCV sequences was detected among
the three patients, suggesting epidemiologic linkage of these
infections (Figure). On separate occasions, patients A and B
underwent dialysis on the same machine following patient C,
during the most likely exposure periods (JanuaryMay 2013
for patient A and November 2009June 2010 for patient B).
Hospitalization events for patients A, B, and C during the
likely exposure periods did not overlap in space and time. No
other common exposures were identified.
No specific event or practice was identified at the dialysis
center that could have led to HCV transmission. However,
the limited infection control practice observation time or
unreported changes in practice between the transmission event
and Tennessee Department of Health infection control observations might have affected these observations. The laboratory
findings, the common station use, and the absence of other
shared exposures support infection of patients A and B during
dialysis at the clinic.
Following CDC recommendations (3) for HCV screening
of dialysis patients by performing anti-HCV testing every
6 months and reporting new anti-HCV seroconversions (4)
to local health departments are important practices for dialysis
clinics. More rigorous HCV screening regimens, combined
with timely reporting of seroconversions to public health officials, will facilitate investigation and infection control improvement recommendations to prevent future infections. Even a
single reported case of acute HCV infection in a hemodialysis
patient warrants health department investigation, because it
might represent intra-facility transmission.
1Tennessee Department of Health; 2End Stage Renal Disease Network 8,
Ridgeland, Mississippi;3Division of Healthcare Quality Promotion, National
Center for Emerging and Zoonotic Diseases, CDC; 4Division of Viral Hepatitis,
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC.
Corresponding author: Daniel Muleta, Daniel.Muleta@tn.gov, 615-532-6633.
FIGURE. Nucleotide variation in hepatitis C quasispecies (E1-HVR1 region, 306 base pairs in length) among six patients* at a dialysis clinic
Tennessee, 2014
Patient A
Patient C
Patient D
Patient B
HCV genotype 1a
Patient E
Nucleotide
variation
5%
Patient F
* Patient Cs hepatitis C test was positive on entry to the dialysis clinic; patients A and B seroconverted after beginning dialysis. Patients D, E, and F are other chronic
hepatitis C-infected patients in treatment at the clinic, and were not genetically linked to the outbreak.
References
1. CDC. Viral hepatitishealthcare-associated hepatitis B and C outbreaks
reported to the Centers for Disease Control and Prevention (CDC)
20082014. Atlanta, GA: US Department of Health and Human Services,
CDC; 2015. Available at http://www.cdc.gov/hepatitis/outbreaks/
healthcarehepoutbreaktable.htm.
2. Messina JP, Humphreys I, Flaxman A, et al. Global distribution and
prevalence of hepatitis C virus genotypes. Hepatology 2015;61:7787.
3. CDC. Recommendations for preventing transmission of infections among

chronic hemodialysis patients. MMWR Recomm Rep 2001;50(No. RR-5).
4. CDC. National Notifiable Diseases Surveillance System: hepatitis C,
acute. Atlanta, GA: US Department of Health and Human Services,
CDC; 2012. Available at http://wwwn.cdc.gov/nndss/conditions/
hepatitis-c-acute/case-definition/2012/.
1387
QuickStats
FROM THE NATIONAL CENTER FOR HEALTH STATISTICS
Birth Rates Among Females Aged 1519 Years, by Race/Ethnicity*

National Vital Statistics System, United States, 1991 and 2014
120
Rate per 1,000 live births
100
1991
2014
80
60
40
20
0
Overall
Asian or
Non-Hispanic American Indian
Pacific Islander
white
or Alaska Native
Hispanic
Non-Hispanic
black
Race/Ethnicity
* For American Indian or Alaska Natives and Asian or Pacific Islanders, includes persons of Hispanic and
non-Hispanic origin.
Data are for U.S. residents only.
From 1991 to 2014, the birth rate for females aged 1519 years declined 61%, from 61.8 to 24.2 births per 1,000, the lowest
rate ever recorded for the United States. Declines ranged from 60% for non-Hispanic white teens to 72% for Asian or Pacific
Islander teens. Despite the declines among all groups, teen birth rates by race/ethnicity continued to reflect wide disparities.
In 1991, rates ranged from 27.3 per 1,000 for Asian or Pacific Islanders to 118.2 for non-Hispanic blacks; in 2014, rates ranged
from 7.7 for Asian or Pacific Islanders to 38.0 for Hispanics.
Source: Hamilton BE, Martin JA, Osterman MJ, et al. Births: final data for 2014. Natl Vital Stat Rep 2015;65(12). Available at http://www.cdc.gov/
nchs/data/nvsr/nvsr64/nvsr64_12.pdf.
Reported by: T.J. Mathews, MS, tmathews@cdc.gov; Brady E. Hamilton, PhD, bhamilton@cdc.gov.
1388
The Morbidity and Mortality Weekly Report (MMWR) Series is prepared by the Centers for Disease Control and Prevention (CDC) and is available free of
charge in electronic format. To receive an electronic copy each week, visit MMWRs free subscription page at http://www.cdc.gov/mmwr/mmwrsubscribe.html.
Paper copy subscriptions are available through the Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402; telephone
202-512-1800.
Readers who have difficulty accessing this PDF file may access the HTML file at http://www.cdc.gov/mmwr/index2015.html. Address all inquiries about the
MMWR Series, including material to be considered for publication, to Executive Editor, MMWR Series, Mailstop E-90, CDC, 1600 Clifton Rd., N.E.,
Atlanta, GA 30329-4027 or to mmwrq@cdc.gov.
All material in the MMWR Series is in the public domain and may be used and reprinted without permission; citation as to source, however, is appreciated.
Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services.
References to non-CDC sites on the Internet are provided as a service to MMWR readers and do not constitute or imply endorsement of these organizations
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