Kevin P. Cain

Tuberculosis Among Foreign-Born Persons in the United States

CONTEXT Foreign-born persons accounted for 57% of all tuberculosis (TB) cases in the United States in 2006. Current TB control strategies have not sufficiently addressed the high levels of TB disease and latent TB infection in this population. OBJECTIVE To determine the risk of TB disease and drug-resistant TB among foreign-born populations and the potential impact of adding TB culture to overseas screening procedures for foreign-born persons entering the United States. DESIGN, SETTING, AND PARTICIPANTS Descriptive epidemiologic analysis of foreign-born persons in the United States diagnosed with TB from 2001 through 2006. MAIN OUTCOME MEASURES TB case rates, stratified by time since US entry, country of origin, and age at US entry; anti-TB drug-resistance patterns; and characteristics of TB cases diagnosed within 3 months of US entry. RESULTS A total of 46,970 cases of TB disease were reported among foreign-born persons in the United States from 2001 through 2006, of which 12,928 (28%) were among recent entrants (within 2 years of US entry). Among the foreign-born population overall, TB case rates declined with increasing time since US entry, but remained higher than among US-born persons--even more than 20 years after arrival. In total, 53% of TB cases among foreign-born persons occurred among the 22% of the foreign-born population born in sub-Saharan Africa and Southeast Asia. Isoniazid resistance was as high as 20% among recent entrants from Vietnam and 18% for recent entrants from Peru. On average, 250 individuals per year were diagnosed with smear-negative, culture-positive TB disease within 3 months of US entry; 46% of these were from the Philippines or Vietnam. CONCLUSION The relative yield of finding and treating latent TB infection is particularly high among individuals from most countries of sub-Saharan Africa and Southeast Asia.

Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies.

Haileyesus Getahun and colleagues report the development of a simple, standardized tuberculosis (TB) screening rule for resource-constrained settings, to identify people living with HIV who need further investigation for TB disease.

An Algorithm for Tuberculosis Screening and Diagnosis in People with HIV

BACKGROUND Tuberculosis screening is recommended for people with human immunodeficiency virus (HIV) infection to facilitate early diagnosis and safe initiation of antiretroviral therapy and isoniazid preventive therapy. No internationally accepted, evidence-based guideline addresses the optimal means of conducting such screening, although screening for chronic cough is common. METHODS We consecutively enrolled people with HIV infection from eight outpatient clinics in Cambodia, Thailand, and Vietnam. For each patient, three samples of sputum and one each of urine, stool, blood, and lymph-node aspirate (for patients with lymphadenopathy) were obtained for mycobacterial culture. We compared the characteristics of patients who received a diagnosis of tuberculosis (on the basis of having one or more specimens that were culture-positive) with those of patients who did not have tuberculosis to derive an algorithm for screening and diagnosis. RESULTS Tuberculosis was diagnosed in 267 (15%) of 1748 patients (median CD4+ T-lymphocyte count, 242 per cubic millimeter; interquartile range, 82 to 396). The presence of a cough for 2 or 3 weeks or more during the preceding 4 weeks had a sensitivity of 22 to 33% for detecting tuberculosis. The presence of cough of any duration, fever of any duration, or night sweats lasting 3 or more weeks in the preceding 4 weeks was 93% sensitive and 36% specific for tuberculosis. In the 1199 patients with any of these symptoms, a combination of two negative sputum smears, a normal chest radiograph, and a CD4+ cell count of 350 or more per cubic millimeter helped to rule out a diagnosis of tuberculosis, whereas a positive diagnosis could be made only for the 113 patients (9%) with one or more positive sputum smears; mycobacterial culture was required for most other patients. CONCLUSIONS In persons with HIV infection, screening for tuberculosis should include asking questions about a combination of symptoms rather than only about chronic cough. It is likely that antiretroviral therapy and isoniazid preventive therapy can be started safely in people whose screening for all three symptoms is negative, whereas diagnosis in most others will require mycobacterial culture.

Yield of Acid-fast Smear and Mycobacterial Culture for Tuberculosis Diagnosis in People with Human Immunodeficiency Virus

RATIONALE The World Health Organization recently revised its recommendations for tuberculosis (TB) diagnosis in people with HIV. Most studies cited to support these policies involved HIV-uninfected patients and only evaluated sputum specimens. OBJECTIVES To evaluate the performance of acid-fast bacilli smear and mycobacterial culture on sputum and nonsputum specimens for TB diagnosis in a cross-sectional survey of HIV-infected patients. METHODS In Thailand and Vietnam, we enrolled people with HIV regardless of signs or symptoms. Enrolled patients provided three sputum, one urine, one stool, one blood, and, for patients with palpable peripheral adenopathy, one lymph node aspirate specimen for acid-fast bacilli microscopy and mycobacterial culture on solid and broth-based media. We classified any patient with at least one specimen culture positive for Mycobacterium tuberculosis as having TB. MEASUREMENTS AND MAIN RESULTS Of 1,060 patients enrolled, 147 (14%) had TB. Of 126 with pulmonary TB, the incremental yield of performing a third sputum smear over two smears was 2% (95% confidence interval, 0-6), 90 (71%) patients were detected on broth-based culture of the first sputum specimen, and an additional 21 (17%) and 12 (10%) patients were diagnosed with the second and third specimens cultured. Of 82 lymph nodes cultured, 34 (42%) grew M. tuberculosis. In patients with two negative sputum smears, broth-based culture of three sputum specimens had the highest yield of any testing strategy. CONCLUSIONS In people with HIV living in settings where mycobacterial culture is not routinely available to all patients, a third sputum smear adds little to the diagnosis of TB. Broth-based culture of three sputum specimens diagnoses most TB cases, and lymph node aspiration provides the highest incremental yield of any nonpulmonary specimen test for TB.

Estimating the Burden of Tuberculosis among Foreign- Born Persons Acquired Prior to Entering the U.S., 2005- 2009

Background The true burden of reactivation of remote latent tuberculosis infection (reactivation TB) among foreign-born persons with tuberculosis (TB) within the United States is not known. Our study objectives were to estimate the proportion of foreign-born persons with TB due reactivation TB and to describe characteristics of foreign-born persons with reactivation TB. Methods We conducted a cross-sectional study of patients with an M. tuberculosis isolate genotyped by the U.S. National TB Genotyping Service, 2005–2009. TB cases were attributed to reactivation TB if they were not a member of a localized cluster of cases. Localized clusters were determined by a spatial scan statistic of cases with isolates with matching TB genotype results. Crude odds ratios and 95% confidence intervals were used to assess relations between reactivation TB and select factors among foreign-born persons. Main Results Among the 36,860 cases with genotyping and surveillance data reported, 22,151 (60%) were foreign-born. Among foreign-born persons with TB, 18,540 (83.7%) were attributed to reactivation TB. Reactivation TB among foreign-born persons was associated with increasing age at arrival, incidence of TB in the country of origin, and decreased time in the U.S. at the time of TB diagnosis. Conclusions Four out of five TB cases among foreign-born persons can be attributed to reactivation TB and present the largest challenge to TB elimination in the U.S. TB control strategies among foreign-born persons should focus on finding and treating latent tuberculosis infection prior to or shortly after arrival to the United States and on reducing the burden of LTBI through improvements in global TB control.

Causes of death in HIV-infected persons who have tuberculosis, Thailand.

Many of these patients die of a cause other than tuberculosis; expanded use of antiretroviral therapy and modern diagnostic technologies may reduce case-fatality rates.

HIV care and treatment factors associated with improved survival during TB treatment in Thailand: an observational study

BackgroundIn Southeast Asia, HIV-infected patients frequently die during TB treatment. Many physicians are reluctant to treat HIV-infected TB patients with anti-retroviral therapy (ART) and have questions about the added value of opportunistic infection prophylaxis to ART, the optimum ART regimen, and the benefit of initiating ART early during TB treatment.MethodsWe conducted a multi-center observational study of HIV-infected patients newly diagnosed with TB in Thailand. Clinical data was collected from the beginning to the end of TB treatment. We conducted multivariable proportional hazards analysis to identify factors associated with death.ResultsOf 667 HIV-infected TB patients enrolled, 450 (68%) were smear and/or culture positive. Death during TB treatment occurred in 112 (17%). In proportional hazards analysis, factors strongly associated with reduced risk of death were ART use (Hazard Ratio [HR] 0.16; 95% confidence interval [CI] 0.07–0.36), fluconazole use (HR 0.34; CI 0.18–0.64), and co-trimoxazole use (HR 0.41; CI 0.20–0.83). Among 126 patients that initiated ART after TB diagnosis, the risk of death increased the longer that ART was delayed during TB treatment. Efavirenz- and nevirapine-containing ART regimens were associated with similar rates of adverse events and death.ConclusionAmong HIV-infected patients living in Thailand, the single most important determinant of survival during TB treatment was use of ART. Controlled clinical trials are needed to confirm our findings that early ART initiation improves survival and that the choice of non-nucleoside reverse transcriptase inhibitor does not.A case study from the Katine parish in Uganda where the challenge of accessing antiretroviral drugs is exacerbated by abject poverty in the region. The article highlights the needs of the community members with HIV / AIDS in the region and the response of AMREF (the NGO working in the region) to addressing these issues.

Antiretroviral therapy for HIV-infected tuberculosis patients saves lives but needs to be used more frequently in Thailand.

Descemet stripping automated endothelial keratoplasty (DSAEK), as coined by myself, is rapidly becoming the most popular method of corneal transplantation for endothelial disease. It is an evolutionary step based on the pioneering work of Melles, with further development by Terry and Price. The advantages of the keratome system to cut donor tissue have not only improved clinical outcomes but also increased the number of corneal surgeons performing endothelial transplantation by eliminating highly skilled and laborious manual dissections. The current decision for a corneal surgeon is no longer DSAEK versus PKP but purchasing a keratome system for approximately

Seasonality of Tuberculosis in the United States, 1993–2008

30,000 versus letting the eye bank supply precut donor tissue (this scenario may change with the availability of less expensive keratome systems or Melles’ newest procedure called Descemet membrane endothelial keratoplasty). Like most expensive purchases, each surgeon must weigh many factors that include patient outcomes, convenience, and cost. This month’s edition of Cornea contains a pertinent article from the Iowa Lions eye bank on the results and surgeon satisfaction of precut donor tissue they supplied to 53 surgeons for 197 DSAEK cases. The favorable conclusions of their surgeon survey deserve further scrutiny. I would like to break down the discussion into 2 categories: clinical outcomes and financial considerations. Clinical outcomes should be the main driving force behind the evaluation of any medical procedure. Safety is the number one priority, but safety is predicated on many factors. Any increase in the number of subsequent intraocular procedures, even with ultimately good outcomes, decreases patient safety. In this survey, donor dislocations ranged from 33% to 20% depending on surgeon’s experience. The authors concluded that these numbers were in line with the previous studies and that there was no increased dislocation rate with precut tissue. I disagree with that conclusion. Although it is true that the original DSAEK papers, mine included, reported high dislocation rates consistent with the numbers in this survey, those were from seminal articles of the authors’ very first cases. Now, several years later, procedural evolution and increased numbers have reduced the present dislocation rate to single digits for experienced surgeons. One could conclude from this survey that precut tissue more than doubles the dislocation rate, which in turn decreases patient safety. To be fair, Chen and Price have reported no increased dislocation rate with precut tissue. Obviously, surgeon’s ability and technique are important factors in all aspects of DSAEK. Surgeon satisfaction should correlate with patient outcomes, especially in a retrospective survey such as the one under discussion. Ninety-eight percent of surgeons were happy with the precut tissue. Closer examination of the reported problems, however, indicates that either this group of surgeons was very easy to please or all the problems were only seen by a single surgeon. Twenty-one donor corneas (11%) required additional manual lamellar dissection by the surgeon to increase the bed size for adequate trephination size. That would make me unhappy. Fourteen cases (8%) failed, with one-third attributable to tissue-related factors. That also would not make me smile. Five donors were reported to be either totally unacceptable or too thick or too thin. I would be unhappy if I received any of those 5 donor tissues. Other annoying problems such as lack of centration mark in corneas or a free-floating anterior cap were reported. Those would be minor irritants. In totaling up all these problems, 98% of surgeons should not have been satisfied. I have never used precut tissue, but based on my discussions with both Drs Terry and Price, I believe that successful outcomes can be equally obtained with precut tissue and surgeon cut tissue. There is a level of security with precut tissue in terms of a post cut cell count and cost accountability in the rare event of an unusable donor from a poor surgeon cut. This leads us into the second half of the discussion, cost.Introduction:The impact of antiretroviral therapy (ART) on HIV-infected tuberculosis (TB) patients in public health programs in resource-limited settings is not well documented due to problems with statistical bias in observational studies. Methods:We measured the impact of ART on survival of HIV-infected TB patients in Thailand using a propensity score analysis that adjusted for factors associated with receiving ART. Results:Of 626 HIV-infected TB patients started on ART during TB treatment, 68 (11%) died compared with 295/643 (46%) of patients not prescribed ART (relative risk 0.24, 95% confidence interval: 0.19 to 0.30); in patients with very low CD4 (<10), 12/56 (21%) patients receiving ART died compared with 35/43 (81%) patients not receiving ART (relative risk 0.26, 95% confidence interval: 0.16 to 0.44). Patients treated in the private sector and in rural areas were less commonly prescribed ART. After controlling for propensity to receive ART, the hazard ratio for death among patients treated with ART was 0.17 (95% confidence interval: 0.12 to 0.24). Discussion:Patients who received ART had one sixth the risk of death of those not receiving ART. The survival benefit persisted even for those with a very low CD4 count. Expanding use of ART in HIV-infected TB patients will require increasing ART use in the private sector and rural areas.

Estimating the impact of newly arrived foreign-born persons on tuberculosis in the United States.

BACKGROUND Although seasonal variation in tuberculosis incidence has been described in several recent studies, the mechanism underlying this seasonality remains unknown. Seasonality of tuberculosis disease may indicate the presence of season-specific risk factors that could potentially be controlled if they were better understood. We conducted this study to determine whether tuberculosis is seasonal in the United States and to describe patterns of seasonality in specific populations. METHODS We performed a time series decomposition analysis of tuberculosis cases reported to the Centers for Disease Control and Prevention from 1993 through 2008. Seasonal amplitude of tuberculosis disease (the difference between the months with the highest and lowest mean case counts), was calculated for the population as a whole and for populations with select demographic, clinical, and epidemiologic characteristics. RESULTS A total of 243 432 laboratory-confirmed tuberculosis cases were reported over a period of 16 years. A mean of 21.4% more cases were diagnosed in March, the peak month, compared with November, the trough month. The magnitude of seasonality did not vary with latitude. The greatest seasonal amplitude was found among children aged <5 years and in cases associated with disease clusters. CONCLUSIONS Tuberculosis is a seasonal disease in the United States, with a peak in spring and trough in late fall. The latitude independence of seasonality suggests that reduced winter sunlight exposure may not be a strong contributor to tuberculosis risk. Increased seasonality among young children and clustered cases suggests that disease that is the result of recent transmission is more influenced by season than disease resulting from activation of latent infection.