TB Elimination-Long Term Follow Up of Certain Contacts

According to a January 1, 2016 FDA Report, preventing tuberculosis (TB) by treating latent Mycobacterium tuberculosis infection (LTBI) is a cornerstone of the U.S. strategy for TB elimination. 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.


The CDC systematically collects aggregate data on contact investigations from the 50 states, the District of Columbia (DC), and Puerto Rico. Data from 2003–2012 were analyzed for trends. During 2003–2012, 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 and 105,100 contacts. Among these contacts, 80.9% were examined; TB was diagnosed in 532 and LTBI in 15,411. Among contacts with LTBI, 65.8% started treatment, and 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 five 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. The reporting cycle lasts more than two years, reflecting the time required for investigation and completion of interventions. 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). The number and types of index patients investigated in the third category are not reported nationally because of jurisdictional variations in policy and practice.


For the period 2003–2012, data from 44 states and Puerto Rico were examined for trends; jurisdictions with gaps in annual reporting were excluded from this analysis. For 2012, data from all 50 states, DC, and Puerto Rico were summarized.


During 2003–2012, 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. 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. The percentage of contacts that were fully examined remained stable at approximately 80%.


INH is the only medication approved by the FDA for TB preventive therapy (i.e., treating LTBI). Regimens of INH monotherapy have been shown to prevent TB in diverse categories of patients, and use of these regimens has been extended based on expert opinion. However, self-supervised daily INH regimens have completion rates of 60% or less in typical settings, attributable largely to the duration of ≥6 months. Rare but severe liver injuries and the concerns over this risk have reduced acceptance of these regimens. Daily rifampin (RIF) for four months for adults and six months for children is recommended when the M. tuberculosis is presumed to be INH-resistant and RIF-susceptible or when INH is contraindicated or is not tolerated by the patient. Rifapentine (RPT), like RIF, is a rifamycin-class antibiotic with an FDA-approved indication for TB disease. Its use for treating LTBI is off label. RPT is microbicidal for susceptible M. tuberculosis. Its long plasma half-life enables infrequent dosing, which can increase DOT convenience and thus adherence. Most RIF-resistant isolates also are resistant to RPT.


During 2003–2012, the reason for not completing treatment was reported for 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), TB disease developed (215), adverse effect of treatment (2,263), health care provider decision (1,859), individual decision (15,173), moved and outcome was unavailable (3,240), or lost to follow-up (10,061).


In 2012, health departments in all 50 states, DC, and Puerto Rico reported 105,100 contacts. 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 smear-negative, 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 = 64–252) TB cases were averted over a five-year span by treating 6,689 contacts with LTBI. 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 128 (34%) of the 376 TB cases that could have been averted in the initial five-year period, if every possible intervention had been completed.


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 two years and requiring specialized skills. 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. The procedures required to confirm TB disease or LTBI can take up to three months. The most common regimen for treating LTBI has been daily isoniazid for nine months, with monthly health care visits for monitoring treatment.


Because the rate of developing TB disease is highest in the first two years following infection, as are the opportunities for preventing TB, TB contact investigations are efficient for finding previously undiagnosed cases and detecting newly acquired LTBI. For the period 2003–2012, for every smear-positive TB patient with contacts elicited, an average of three contacts with LTBI were found, and for every ten smear-positive TB patients with contacts elicited, one contact had TB disease. 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. 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. For settings with more resources, larger and more intensive contact investigations are recommended.


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 five 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.


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 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, efforts should be made to ensure that contacts are elicited from all potentially infectious patients. Second, one in five contacts was 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, but one third of persons with LTBI did not start treatment, possibly because of patient or health care provider misperceptions about risks and benefits of treatment for LTBI. Furthermore, one third of all infected contacts who started treatment did not complete it.


A major barrier to completing treatment has been the nine-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, and innovative case management strategies building on collaborations between health care systems could minimize loss to follow-up and ensure treatment completion. Increasing the treatment of LTBI for multiple risk groups, including contacts recently infected with M. tuberculosis, is essential for achieving TB elimination.


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 five 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. 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.


See the CDC Report


See the earlier CDC Report on TB Treatment


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