Updates
By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
TB in Undocumented Immigrants
Source: Achkar JM, et al. Differences in clinical presentation among persons with pulmonary tuberculosis: a comparison of documented and undocumented foreign-born versus US-born persons. Clin Infect Dis. 2008;47;1277-1283.
Concerns have been raised that immigrants, especially those who are undocumented, afraid of deportation or who have limited financial resources, may be reluctant to present for care, thus compounding the risk for contagious diseases.
Achkar et al conducted a cross-sectional survey of 194 persons with culture-confirmed pulmonary tuberculosis, examining differences in their presentation. Patients were grouped according to whether they were US-born (31%), documented foreign born (32%), or undocumented foreign-born (37%). Of those born in the United States, 87% were unemployed, 50% were HIV+, and 25% were homeless. In contrast, foreign-born persons with pulmonary TB were less likely to be unemployed (62%), HIV+ (16 % of those tested), or homeless (7.5%). Foreign-born patients were largely Asian, whereas most of the US-born patients were black or Hispanic.
About two-thirds of the patients in each of the groups presented with multi-lobar disease or miliary infiltrates, 56%-66% presented with positive smears, and more than a third in each group had cavitary disease. The degree of infectivity, as measured by smear positivity, also was similar. Foreign-born persons did present with a greater frequency of hemoptysis (p = .018) and a longer duration of cough, compared with US-born persons (8 vs 4 weeks, p = .023). This suggests that foreign-born persons may have been infective for a longer period of time prior to presentation.
If we are to combat tuberculosis and other transmissible infections in this country, maintaining our public health infrastructure is essential. Actions that discourage patients from accessing care, or limiting public health funding, affect us all.
Treatment of LTBI — Is INH It?
Source: Menzies D, et al. Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent tuberculosis infection. Ann Intern Med. 2008;149:689-697.
Data suggest that fewer than 50% of persons offered INH treatment for LTBI complete their course of treatment. Savvier patients often ask me why they have to take INH for nine months, when their family member receives treatment for active TB for six months. And, in the age of the internet, it is not uncommon for patients to ask me if I've ever heard of rifampin for four months as an alternative?
These authors did a head-to-head safety comparison of isoniazid (5 mg/kg, up to 300 mg daily) administered for nine months, vs rifampin (10 mg/kg, up to 600 mg daily) administered for four months to adults (>18 years of age) with LTBI. Patients at risk for hepatotoxicity were excluded. The major endpoints were adverse events and the time to completion of therapy. Laboratory safety studies were performed monthly for the first four months, and then approximately every six weeks at the discretion of the treating physician. Grade 3 hepatoxicity was defined as a symptomatic elevations of AST or ALT 3-10 times the upper limit of normal (ULN) or asymptomatic elevations of AST or ALT 5-10 times the ULN; grade 4 hepatotoxicity was defined as elevations of AST or ALT > 10 times the ULN.
Of 827 patients randomized to receive treatment, 60% completed treatment with INH and 78% completed treatment with rifampin (p < .0001). Adverse events due to study therapy were similar between the two groups. Grade 3 or 4 events occurred, however, significantly more often in patients started on INH than those started on rifampin (4.0% vs 1.7%, p = .003). Virtually all of this was due to hepatotoxicity, most of which occurred within the first 4-8 weeks of treatment. Drops in platelet and white blood cell counts occurred more frequently in rifampin recipients; 2% dropped their platelet count by > 100 x 109 cells/L, and 10% had drops of > 2.5 WBCs x 109 cells/L. Rash also was more frequent in patients receiving rifampin compared with INH (1.9% vs 1.2%).
Even for those patients without side effects, the rate of completion for patients starting rifampin was higher than those started on INH (91% vs 74%).
The frequency of serious liver test abnormalities due to INH in this study was higher than in others, although regular monthly screening was adequate to detect serious abnormalities before patients were harmed, and all liver test abnormalities resolved in those patients who submitted to follow-up testing.
While the use of rifampin for four months may seem like an attractive alternative, there are good reasons not to choose this agent for the treatment of LTBI. First, there are no studies documenting its efficacy for LTBI. Second, the incidence of rifampin resistance is not negligible and is rising in many parts of the United States (and the world); in our county, the risk of rifampin resistance is about 17%, compared with 4% for INH. Rifampin has important drug interactions and is a potent inducer of the P-450 cytochrome system. Not mentioned in the accompanying editorial is the risk of promoting rifampin resistance among gram positive organisms, especially methicillin-resistant S. aureus. For the latter reason alone, the broader use of rifampin for the treatment of LTBI should be discouraged. Clearly, other effective and tolerable agents are needed in the treatment of persons exposed to tuberculosis.
Public Good vs Individual Rights?
Source: Federal air travel restrictions for public health purposes — United States, June 2008-May 2008. MMWR Morb Moral Wkly Rep. 2008,57:1009-1012.
I had the opportunity last year to provide care for a 28-year-old Asian-Indian man working in Silicon Valley, who presented to urgent care one evening with multilobar cavitary lung disease, consistent with pulmonary TB. He had significant weakness and spasticity of his lower extremities, and proved to have Pott's disease involving multiple vertebrae of the thoracic and lumbar-sacral spine. He had first developed weakness in his left leg two years earlier while in India, but was told he did not have TB because a TST was negative, and instead received antibiotics for spinal osteomyelitis.
He had entered this country only six months earlier on a work visa as a contract employee for a high-tech company, and was living with four other young men in a one bedroom apartment. By the time he presented, he had been cough for two months and was cachectic — he reported being so cold at work, he would sit at his desk wearing a blanket.
His isolate was susceptible to all five first-line agents tested. But with 4+ AFB smears, and nowhere to go, he remained hospitalized in isolation for seven weeks, until he became smear-negative. Throughout his hospitalization, despite repeated explanations regarding the communicability of his condition, he begged to be allowed to fly home to his parents in Indai — and at one point, was found to have purchased e-tickets for a flight home. He'd already proven himself unreliable by taking the bus home after his urgent care appointment, and failed for two days to present to hospital for admission as instructed.
Eventually discharged, and still culture positive, his company kindly stepped in and put him up in an apartment (his roommates — all skin test positive — refused to take him back). During a phone call to secure authorization for payment for a follow-up MRI, I learned he had convinced his company to purchase tickets for him to travel back to India! After phoning the public health department, he was placed on a "no fly list," now called the Do Not Board (DNB) List, and not removed until cultures were negative after ~ 4 months of therapy. He promptly left the United States, and has not been heard from since.
The Public Health DNB List was created in 2007, and is overseen by the CDC and the Department of Homeland Security, to provide a mechanism for restricting commercial air travel for persons deemed a public health threat. In order to place someone on the list, a physician can contact their Public Health Department (PHD), and determine if the patient meets requisite criteria. Criteria include the severity of the public health threat and the communicability of the infection, the potential for nonadherence, and the flight risk of the individual.
From June 2007 to May 2008, the CDC received requests to include 42 persons on the DNB, 33 (79%) of which were granted. Most (85%) of the requests came from PHDs within the United States, although one request came from the State Department, 3 from Canada, and one from Mexico. Fourteen of 33 persons were outside of the United States when placed on the list. Two persons were known to have attempted air travel despite warnings not to do so. Of the remaining nine persons, two were deemed to be non-contagious, three voluntarily agreed not to fly, and four were subject to other local isolation procedures.
All 33 patients placed on the DNB list had probable or documented TB, their median age was 41 years, and 61% were male. TB organisms, available from 27 persons, were susceptible to first line therapy. By May 2008, half of the patients had already been removed from the list, including my patient, and were allowed to travel. Permission to remove someone from the list is generally granted within 24 hours of a request.
Concerns have been raised that immigrants, especially those who are undocumented, afraid of deportation or who have limited financial resources, may be reluctant to present for care, thus compounding the risk for contagious diseases.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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