# Presentation: 718923

## Epidemiology of Pediatric Tuberculosis in the United States, 1993–2006

**Surveillance, Epidemiology, and **
**Outbreak Investigations Branch**
**Division of Tuberculosis Elimination**
**Centers for Disease Control and Prevention (CDC)**

## Pediatric TB—Background

**Definition of pediatric tuberculosis (TB):****TB disease in a person <15 years old**** **
**In 2006,**
**13,779 TB cases were reported among all age groups **
**807 (5.9%) were pediatric  **

**Notes:**
Tuberculosis (TB) is a reportable condition in all United States jurisdictions, and TB cases are reported to CDC in a standard format by public health authorities throughout the United States. These reports are summarized for pediatric cases in this slide set, for the years 1993 through 2006.
Pediatric TB is defined as TB disease in a person < 15 years old.  The age group of “pediatric TB” is consistent with the convention used by the Division of HIV/AIDS Prevention, NCHHSTP, CCID, CDC. 
Pediatric TB is a public health problem of special significance. When children have TB disease, it indicates recent transmission, as time-bound by their date of birth, and usually primary disease (from infection within the past 3–12 months), unlike when adults have TB disease, which often reflects reactivation of remotely acquired infection.  In 2006, there were 13,779 cases of TB reported among all age groups, 807 (5.9%) were pediatric. 

## TB Case Definition and Verification

**  ****Incident case of disease**
**  ****Case verification categories:**
**1)  Laboratory confirmed cases-”Gold Standard”**
**-  Positive culture, DNA probe, or nucleic  acid amplification test**
**-  Positive AFB smear when culture not attainable**
**2)  Clinical case definition**
**	****      ****-  Positive tuberculin skin test ****	****	**** **
**	****      ****-  Signs and symptoms of TB disease**
**	****      ****-  Current treatment for TB disease**
**3)**** **** Provider diagnosis:**
**	****      ****-  Diagnosed by health care provider**
**	****      ****-  Does not fulfill all criteria necessary to**
**	****	****     ****meet laboratory or clinical case**
**	****	****     ****definitions**

**Notes:**
Reports of TB are counted according to a set of criteria (the “case definition”) which is specific to the United States. Only incident cases that are diagnosed in the United States are included, and cases are verified by three levels of certainty, depending on the types of information that are available to healthcare practitioners and public health authorities. The verification of cases is an interactive process between healthcare practitioners and public health authorities and between public health authorities and CDC.
The verification of cases is especially important when considering the epidemiology of TB in children because a smaller fraction of cases among this age group are confirmed by bacteriology. Therefore, the statistics for children are more sensitive to changes in medical practice and notification than they are for adults.

## TB Cases, All Ages, by Age Group, 1993–2006

**Year**

**TB Cases**

**Notes:**
The number of TB cases in the United States has been decreasing for each age grouping. The relative changes are less apparent for the two younger age groups because the number of cases is smaller. 

## TB Case Rates, All Ages, by Age Group1993–2006

**Year**

**TB Case Rate per 100,000**

**Note:  Rates presented on a logarithmic scale**

**Notes:**
When the TB case rates are shown on a logarithmic scale, the relative trends can be compared by inspection. Straight lines with a negative (i.e., downward) slope demonstrate a constant decline (i.e., exponential decay or rate of decrease). The pattern for the overall United States (white line), 1994–2000, is a good example of this. After 2000, the decline for the overall United States slowed.
Lines that track in parallel show a stable rate ratio. In this figure, the decline of the pediatric TB case rate (yellow line) is very similar to the rate for the overall United States (white line), with divergence in 2005–2006. The rate for the 15–24-year age group is declining at the slowest rate, and it is almost static after 2002. This probably is related to the increasing preponderance of cases in foreign-born persons, and it could influence the pediatric rate when immigrants have children in the United States and these children are exposed in their households. 

## Percent of Pediatric TB Cases by Age Group1993–2006N=15,946

**Notes:**
The pediatric age group (< 15) can be divided into four groups that reflect age-dependent differences in TB pathophysiology that have been noted historically:
Age < 1: Infancy. Cases in this age group represent the most recent transmission and also are slightly more likely to be the severe forms of disease that were uniformly fatal before the discovery of chemotherapy.
Age 1–4: Toddler/preschool. In this transitional age group, primary pulmonary TB is the most common form, and self-resolution of recent infection is a greater possibility.
Age 5–9: School age. In this age group, primary pulmonary TB is the expected form of disease, but rare instances of contagious adult form/reactivation disease are reported.
Age 10–14: Early adolescence. Another transitional period, where disease patterns more similar to adult forms become more prevalent.

## Pediatric TB Cases by Age Group 1993–2006N=15,946

**Year**

**TB Cases**

**Notes:**
Overall, the number of TB cases in all the division of the pediatric age group have decreased, 1993–2006.

## TB Case Rates by Pediatric Age Groups 1993–2006N=15,946

**Year**

**TB Case Rate per 100,000**

**Note:  Rates presented on a logarithmic scale**

**Notes:**
The population-adjusted rates have been consistently greatest for the toddler/preschool age group, followed by the infant group. The logarithmic view of the case rates shows that the trend of decreasing in case rates varied from year to year but was similar overall among the groups.

## Pediatric TB Cases by Race/Ethnicity 1993–2006N=15,946

**Year**

**Pediatric TB Cases**

**Notes:**
By the standard categories of race and ethnicity, the greatest number of cases in recent years has been among Hispanic children.

## Pediatric TB Case Rates by Race/Ethnicity 1993–2006N=15,946 

**TB Case Rate per 100,000**

**Rates presented on a logarithmic scale.                                                             **
**American Indian/Alaska Native rate not shown because of small denominators**

**Notes:**
A very different picture emerges when the case counts are population adjusted to annual rates. The rates among all groups except white, nonHispanic are similar, and the trends (i.e., slopes of the trend lines) for decreasing rates also are similar.
Rates are not shown for American Indian/Alaska Native children because the small case counts and small denominators give an unstable trend line.

## TB Case Rates by Pediatric Age GroupsU.S.-born and Foreign-born, 1994–2006N=14,285

**Year**

**TB Case Rate per 100,000**

**Note:   Rates presented on a logarithmic scale.  Data not available before 1994.**
**USB = U.S.-born, FB=Foreign-born**

**Foreign-born**** **

**U.S.-born**

**Notes:**
Important patterns of rate trends are shown by the comparison of the age groups separated into foreign born and U.S. born.
Within the two sets of age groups, when grouped by origin, the relative rates among ages is similar. For example, the early adolescence group (green lines) has the lowest rates for both foreign born and U.S. born.
For any specific age group, the difference in rates between U.S. born and foreign born is an order of magnitude. That is, the incidence rate is 10 times greater for foreign-born children in any age group.
The decline in case rates is similar among all the groups. That is, the lines are approximately parallel, and no consistent pattern of divergence is noted.
Some of the trend lines are erratic because of small numbers of cases and small denominators.

## Number and Percent Foreign-born Pediatric TB Cases, 1993–2006

**Number of Pediatric TB Cases**

**Percent**

**Notes:**
In contrast to overall U.S. TB cases, less than half of pediatric cases are among foreign-born children, and the fraction has been fairly stable since 1993. The complicating factor of TB in U.S.-born children of foreign-born parents cannot be differentiated by current surveillance methods, but it is a subject of current studies and for future surveillance systems.

## Foreign-born Pediatric TB Cases by Birth Country* and 4-Year Interval, 1995–2006N=3,231

| Mexico (467) | Mexico (375) | Mexico (323) |
| --- | --- | --- |
| Philippines (118) | Somalia (79) | Somalia (65) |
| Viet Nam (73) | Philippines (67) | Philippines (63) |
| Somalia (43) | Haiti (38) | Haiti (45) |
| Haiti (39) | Viet Nam (36) | Viet Nam (37) |
| Russia (38) | Sudan (26) | India (36) |
| Other (422) | Other (417) | Other (424) |
|  |  |  |

***Ranked by counts**

**Notes:**
For comparison, the counts from consecutive 4-year intervals are compared. Mexico has remained the commonest country of origin for foreign-born children who have TB reported in the United States. The Philippines has remained near the top of the list, and Somalia has increased in prominence. 

## States with the Greatest Percent of the National Total Pediatric TB Cases, 1993–2006N=15,946 

**Notes:**
The state with the greatest number of TB cases, 1993–2006, is California, with 25.2% of the cases during the interval.

## States with Greatest Numbers of Pediatric TB Cases, 1993–2006

** *****Average percent of total state cases that are pediatric, for all years**
****Time-averaged annual rate per 100,000**

| California |      4,025 |        7.7 |       3.7 |
| --- | --- | --- | --- |
| Texas |      1,874 |        7.3 |       2.7 |
| New York |      1,399 |        4.8 |       2.6 |
| Florida |         794 |        4.4 |       1.9 |
| Illinois |         791 |        6.9 |       2.1 |
| Georgia |         700 |        7.8 |       2.8 |
| All Others |      6,363 |        5.9 |       1.3 |

**State****	**

**Number**

**Percent***

**Rate****

**Pediatric TB Cases**

**Overall U.S.**

**15,946**

**6.3**

**1.9**

**Notes:**
Of these six states with the greatest numbers of pediatric cases, 1993–2006, California, Texas, Illinois, and Georgia exceed the national average fraction of cases that were in the pediatric age group: 6.3%. All six states matched or exceeded the national average (time-averaged) annual incidence rate for pediatric TB: 1.9 per 100,000 population.

## States with Greatest Percent of Pediatric TB cases, 1993–2006

***Average percent of total state cases that are pediatric, for all years**
****Time-averaged rate per 100,000**

| Alaska |           125 |      13.0 |       5.7 |
| --- | --- | --- | --- |
| Rhode Island |             72 |      10.4 |       2.6 |
| Minnesota |           253 |        9.8 |       1.7 |
| Oklahoma |           262 |        9.8 |       2.6 |
| Delaware |             52 |        9.7 |       2.4 |
| Arizona |           361 |        9.3 |       2.3 |
| All Others |      14,821 |        6.1 |       1.9 |

**State****	**

**Number**

**Percent***

**Rate****

**Pediatric TB Cases**

**Overall U.S.**

**15,946**

**6.3**

**1.9**

**Notes:**
However, the states with the most pediatric cases are not in the list of those with the greatest time-averaged percentage of their cases in the pediatric age group, which is headed by Alaska.

## States with Greatest Rate of Pediatric TB Cases, 1993–2006

***Average percent of total state cases that are pediatric, for all years**
****Time-averaged rate per 100,000**
**†****D.C. (District of Columbia) is a distinct reporting jurisdiction**

| Alaska |        125 |      13.0 |       5.7 |
| --- | --- | --- | --- |
| D.C.† |          54 |        4.0 |       4.0 |
| California |     4,025 |        7.7 |       3.7 |
| Georgia |        700 |        7.8 |       2.8 |
| Texas |     1,874 |        7.3 |       2.7 |
| Arkansas |        204 |        8.2 |       2.6 |
| All Others |     8,964 |        5.5 |       1.5 |

**State****	**

**Number**

**Percent***

**Rate****

**Pediatric TB Cases**

**Overall U.S.**

**15,946**

**6.3**

**1.9**

**Notes:**
Alaska also reports the greatest incidence rate of pediatric TB and is followed by the District of Columbia.

## Pediatric TB Cases by Case Verification Criterion*, 1993–2006N=15,946

**Pediatric TB Cases by ****Case Verification Criterion*, 1993–2006****N=15,946**

**Provider Diagnosis **
**24%**

**Clinical Case Definition  51%**

**Laboratory confirmed 25%**

** *****Based on the public health surveillance definition for TB [*****MMWR *****1997:46(No. RR-10):40-41]**

**Notes:**
Slightly more than a half of pediatric TB cases are verified by the clinical case definition only, and slightly less than a quarter of cases have bacteriological confirmation, and this is matched by the fraction that are counted because of the decision of a medical provider, which has the least specific verification criteria. Furthermore, these proportions are different for the subgroups of pediatric age that were defined for earlier slides in this series.

## Pediatric TB Cases by Case Verification Criterion, 1993–2006N=15,946

**Laboratory Confirmed**

**Clinical Case**

**Provider Diagnosis**

**Notes:**
Provider diagnosis is common for all the pediatric age groups, but least common in the preadolescent group. Laboratory confirmation is most common for the infancy age group and least common for the school-age group.

## Pediatric TB Cases by Site of Disease, 1993–2006

**Any extrapulmonary involvement* **
**                  ****(totaling 28.9%)**
**          ****Lymphatic****	****    18.9%**
**          ****Meningeal****	****      3.1%**
**          ****Miliary****	****      1.5% **
**          ****Bone & Joint****	****      1.5%**
**          ****Other****	****      3.9%****     ****	**

***Any extrapulmonary involvement which includes cases that are extrapulmonary only and both**
**Patients may have more than one disease site but are counted in mutually exclusive categories for **
**surveillance purposes. **

**Notes:**
TB most typically is a pulmonary disease, but the infection can manifest in any organ system. More than a quarter of pediatric cases involve a extrapulmonary site. Of these sites, disease in the lymphatic system is most common.

## Percent of Pediatric TB Cases by Site of Disease*, 1993–2006N=15,946

**Pulmonary**

**Extrapulmonary**

**Both**

**Notes:**
The fraction of pediatric TB cases with extrapulmonary involvement varies by the age subgroups. The preadolescent group is most likely to have extrapulmonary disease alone and at least an extrapulmonary site of disease, but the infant group is most likely to have combined pulmonary and extrapulmonary disease.

## Percent of Pediatric TB Cases with Any Extrapulmonary Involvement* by Age Group and Selected Sites of Disease, 1993–2006N=15,946

| Lymphatic | 8.0 | 19.3 | 22.3 | 19.2 |
| --- | --- | --- | --- | --- |
| Meningeal | 7.5 | 3.5 | 1.4 | 1.8 |
| Miliary | 5.6 | 1.2 | 0.6 | 1.2 |
| Bone & Joint
 | 0.3 | 1.3 | 1.7 | 2.4 |
| Other | 3.4 | 2.6 | 3.9 | 8.3

 |

**Site of Disease**

** ****Age < 1**
**(n=1,471)**

** ****Age 1-4**
**(n=7,884)**

** ****Age 5-9**
**(n=3,691)**

** ****Age 10-14**
**  ****(n=2,900)**

**Total**

**24.8**

**27.9**

**29.9**

**32.9**

***Any extrapulmonary involvement includes extrapulmonary only and both**
**Note:  Combine the total extrapulmonary percent shown with the pulmonary percent in slide #21 to obtain 100% for each age group. **

**Notes:**
When the extrapulmonary sites are compared by age group, disease in the lymphatic system is the commonest form in all age groups. Disseminated disease, represented by miliary TB, and disease of the central nervous system are commoner in the younger age groups, while bone and joint disease is commonest in the preadolescent group.

## Percent of TB Cases in Children Age < 1 Year With Any Extrapulmonary Involvement, 1993–2006N=1,471

| Lymphatic | 7.2% | 17.7% |
| --- | --- | --- |
| Meningeal | 7.8% | 3.5% |
| Miliary | 5.8% | 3.5% |
| Bone & Joint | 0.3% | 0.9% |
| Other | 3.4% | 1.8% |

_**Site of disease**_

_**U.S.-born**_

_**Foreign-born**_

**Total****	**

**24.5%***

**27.4%***

***Any extrapulmonary involvement includes extrapulmonary only and both**** **

**Notes:**
Foreign-born infants with TB are more likely to have at least one extrapulmonary site of disease, and of these sites, the lymphatic system is much more common than it is for U.S.-born children. U.S.-born children have a greater fraction of disease in the central nervous system. The reasons for these differences are unknown.

## Percent of TB Cases in Children Age 1 - 4 Years With Any Extrapulmonary Involvement, 1993–2006N=7,884

| Lymphatic | 19.4% | 19.0% |
| --- | --- | --- |
| Meningeal | 3.8% | 2.0% |
| Miliary | 1.3% | 1.0% |
| Bone & Joint | 1.1% | 2.0% |
| Other | 2.7% | 2.0% |

_**Site of disease**_

_**U.S.-born**_

_**Foreign-born**_

**Total****	**

**28.3%***

**26.0%***

***Any Extrapulmonary involvement includes extrapulmonary only and both**** **

**Notes:**
Differences for the older groups are less pronounced. For the toddler/preschool group, disease of the central nervous system still is greater for U.S.-children than for foreign-born children, but the difference is not as pronounced as it is for infants.

## Percent of TB Cases in Children Age 5 - 9 Years With Any Extrapulmonary Involvement, 1993–2006N=3,691

| Lymphatic | 23.1% | 20.8% |
| --- | --- | --- |
| Meningeal | 1.4% | 1.0% |
| Miliary | 0.6% | 0.6% |
| Bone & Joint | 1.6% | 2.1% |
| Other | 4.1% | 3.8% |

_**Site of disease**_

_**U.S.-born**_

_**Foreign-born**_

**Total****	**

**30.8%***

**28.3%***

***Any Extrapulmonary involvement includes extrapulmonary only and both**** **

**Notes:**
The patterns for extrapulmonary TB in school age children are similar to those of the pre-school age group, with a slightly greater percentage for lymphatic disease in both U.S.-born and foreign-born children.

## Percent of TB Cases in Children Age 10-14 Years With Any Extrapulmonary Involvement, 1993–2006N=2,900

| Lymphatic | 20.4% | 18.1% |
| --- | --- | --- |
| Meningeal | 1.6% | 1.8% |
| Miliary | 1.5% | 0.8% |
| Bone & Joint | 2.0% | 2.8% |
| Other | 9.0% | 7.3% |

_**Site of disease**_

_**U.S.-born**_

_**Foreign-born**_

**Total****	**

**34.5%***

**30.8%***

***Any Extrapulmonary involvement includes extrapulmonary only and  both**** **

**Notes:**
Among children 10-14 years old, the fraction of cases that are extrapulmonary is still greater, with a persistent predominance in U.S.-born children.  Lymphatic sites are diminished somewhat, and all other categories account for the overall increase.

## Pediatric TB Cases by HIV Status, 1993–2005*N=14,990

**Information on HIV result is not available for the majority of pediatric TB cases (80.7%)**** **
**Percent of pediatric TB cases with HIV-positive test results, minimum estimate** (1.0%)**
**Percent of pediatric cases with HIV-positive test results of those patients with known results (5.1%)**

***California HIV data through 2004 only**
****Pediatric TB cases with positive HIV test results divided by all pediatric TB cases . **
**California only reports positive HIV test results based on TB and AIDS registry matching; all other California TB **
**cases are classified as “Unknown.”**

**Notes:**
TB is an indicator disease for HIV infection, but the rate of testing in pediatric TB cases that is reported with surveillance results is low: less than 20%. The minimum estimate is 1%, that is, 1% of reported cases include the notice of a positive HIV test result. However, of the subset of cases that include an HIV test result, more than 5% have a positive result.
All TB patients, regardless of age, should be offered opt-out testing for HIV infection, in accordance with national guidelines.

## Number and Percent of Culture-confirmed Pediatric TB Cases with Drug Resistance, 1993–2005

**First line drugs are Isoniazid, Rifampin, Pyrazinamide and Ethambutol**
**MDR TB = resistance to at least Isoniazid and Rifampin **

**Notes:**
Drug resistance results are possible only for TB cases that are confirmed by culture results, and the rates that are shown here are based on those cases. That fraction of cases with resistance to at least one drug has increased through 2005, the most recent year with complete reporting. The reason for this trend is not known. However, the fraction of cases with multidrug resistance, that is, resistance to at least isoniazid and rifampin, has remained small and stable.

## Pediatric TB Cases by Use of Directly Observed Therapy (DOT), 1993–2004N=14,233*

**Year**

**Percentage**

** *****Pediatric TB cases with patient alive at diagnosis and started on treatment**

**Notes:**
The American Thoracic Society, the American Academy of Pediatrics, and CDC strongly recommend directly observed therapy for all TB patients. DOT means that the ingestion of each dose of medication is observed by a trained worker, who should not be a family member. The fraction of pediatric cases with DOT reported has increased since 1993.

## Pediatric TB Cases by Treatment Outcome 1993–2004N=14,233*

| Completed treatment          13,459 | 94.6 |
| --- | --- |
| Moved                                        352 | 2.5 |
| Lost to follow-up                      138 | 1.0 |
| Died                                             78 | 0.6 |
| Other**                                      206 | 1.3 |

**Outcome**

**%**

**Note:  Cause of death not recorded in TB case reports**
** *****Pediatric TB cases with patient alive at diagnosis and started on treatment**
****Other includes refused, other, unknown and missing **

**Cases**

**Notes:**
The treatment-completion rate is high: 94.6% averaged over the years with final treatment data. Death is an uncommon reason for the end of treatment, although the death rate of 0.6% is greater than expected for a population in this age group. (For all age groups, in the United States death is the reason that therapy is stopped for approximately 7–8% of TB patients.)

## Deaths Occurring Among Pediatric TB Cases, by Age Group, 1993–2004N=14,282

**Note:  Cause of death not recorded in TB case reports**
****Death includes died during therapy or dead at TB diagnosis **

|  Age < 1 | 1298 | 26 | 2.0 |
| --- | --- | --- | --- |
|  Age 1-4 | 7094 | 46 | 0.6 |
|  Age 5-9 | 3334 | 20 | 0.6 |
|  Age 10-14 | 2556 | 20 | 0.8 |

**  ****Age Group****	****         Cases                Deaths**         % of Cases**

**Notes:**
However, death associated with a report of TB is more common for the youngest age group, infants. For the statistics shown here, death at the time of diagnosis (i.e., before treatment is started) and during treatment are combined. Cause of death is not included in TB case reports.