The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is ...excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule.
We identified 12 studies that had systematically collected sputum specimens regardless of signs or symptoms, at least one mycobacterial culture, clinical symptoms, and HIV and TB disease status. Bivariate random-effects meta-analysis and the hierarchical summary relative operating characteristic curves were used to evaluate the screening performance of all combinations of variables of interest. TB disease was diagnosed in 557 (5.8%) of 9,626 people living with HIV. The primary analysis included 8,148 people living with HIV who could be evaluated on five symptoms from nine of the 12 studies. The median age was 34 years. The best performing rule was the presence of any one of: current cough (any duration), fever, night sweats, or weight loss. The overall sensitivity of this rule was 78.9% (95% confidence interval CI 58.3%-90.9%) and specificity was 49.6% (95% CI 29.2%-70.1%). Its sensitivity increased to 90.1% (95% CI 76.3%-96.2%) among participants selected from clinical settings and to 88.0% (95% CI 76.1%-94.4%) among those who were not previously screened for TB. Negative predictive value was 97.7% (95% CI 97.4%-98.0%) and 90.0% (95% CI 88.6%-91.3%) at 5% and 20% prevalence of TB among people living with HIV, respectively. Abnormal chest radiographic findings increased the sensitivity of the rule by 11.7% (90.6% versus 78.9%) with a reduction of specificity by 10.7% (49.6% versus 38.9%).
Absence of all of current cough, fever, night sweats, and weight loss can identify a subset of people living with HIV who have a very low probability of having TB disease. A simplified screening rule using any one of these symptoms can be used in resource-constrained settings to identify people living with HIV in need of further diagnostic assessment for TB. Use of this algorithm should result in earlier TB diagnosis and treatment, and should allow for substantial scale-up of IPT.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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.
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Kevin Cain and colleagues reflect on the cross border movement of people from Somalia with MDR-TB and the implications for MDR-TB programs in East Africa.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mortality from TB continues to be a global public health challenge. TB ranks alongside Human Immunodeficiency Virus (HIV) as the leading infectious causes of death globally. HIV is a major driver of ...TB related morbidity and mortality while TB is the leading cause of mortality among people living with HIV/AIDS. We sought to determine excess mortality associated with HIV and the effect of antiretroviral therapy on reducing mortality among tuberculosis patients in Kenya.
We conducted a retrospective analysis of Kenya national tuberculosis program data of patients enrolled from 2013 through 2014. We used direct standardization to obtain standardized mortality ratios for tuberculosis patients compared with the general population. We calculated the population attributable fraction of tuberculosis deaths due to HIV based on the standardized mortality ratio for deaths among TB patients with HIV compared to TB patients without HIV. We used Cox proportional hazards regression for assessing risk factors for mortality.
Of 162,014 patients included in the analysis, 6% died. Mortality was 10.6 (95% CI: 10.4-10.8) times higher among TB patients than the general population; 42% of deaths were attributable to HIV infection. Patients with HIV who were not receiving ART had an over four-fold risk of death compared to patients without HIV (aHR = 4.2, 95% CI 3.9-4.6). In contrast, patients with HIV who were receiving ART had only 2.6 times the risk of death (aHR = 2.6, 95% CI 2.5-2.7).
HIV was a significant contributor to TB-associated deaths in Kenya. Mortality among HIV-infected individuals was higher among those not on ART than those on ART. Early initiation of ART among HIV infected people (a "test and treat" approach) should further reduce TB-associated deaths.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To assess the performance of symptom-based screening for tuberculosis (TB), alone and with chest radiography among people living with HIV (PLHIV), including pregnant women, in Western Kenya.
...Prospective cohort study.
PLHIV from 15 randomly-selected HIV clinics were screened with three clinical algorithms World Health Organization (WHO), Ministry of Health (MOH), and "Improving Diagnosis of TB in HIV-infected persons" (ID-TB/HIV) study, underwent chest radiography (unless pregnant), and provided two or more sputum specimens for smear microscopy, liquid culture, and Xpert MTB/RIF. Performance of clinical screening was compared to laboratory results, controlling for the complex design of the survey.
Overall, 738 (85.6%) of 862 PLHIV enrolled were included in the analysis. Estimated TB prevalence was 11.2% (95% CI, 9.9-12.7). Sensitivity of the three screening algorithms was similar WHO, 74.1% (95% CI, 64.1-82.2); MOH, 77.5% (95% CI, 68.6-84.5); and ID-TB/HIV, 72.5% (95% CI, 60.9-81.7). Sensitivity of the WHO algorithm was significantly lower among HIV-infected pregnant women 28.2% (95% CI, 14.9-46.7) compared to non-pregnant women 78.3% (95% CI, 67.3-86.4) and men 77.2% (95% CI, 68.3-84.2). Chest radiography increased WHO algorithm sensitivity and negative predictive value to 90.9% (95% CI, 86.4-93.9) and 96.1% (95% CI, 94.4-97.3), respectively, among asymptomatic men and non-pregnant women.
Clinical screening missed approximately 25% of laboratory-confirmed TB cases among all PLHIV and more than 70% among HIV-infected pregnant women. National HIV programs should evaluate the feasibility of laboratory-based screening for TB, such as a single Xpert MTB/RIF test for all PLHIV, especially pregnant women, at enrollment in HIV services.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
In Kenya, the comparative incidences of tuberculosis among persons with and without HIV have not been described, and the differential impact of public health interventions on tuberculosis incidence ...in the two groups is unknown.
We estimated annual tuberculosis incidence stratified by HIV status during 2006-2012 based on the numbers of reported tuberculosis patients with and without HIV infection, the prevalence of HIV infection in the general population, and the total population. We also made crude estimates of annual tuberculosis incidence stratified by HIV status during 1998-2012 by assuming a constant ratio of HIV prevalence among tuberculosis patients compared to the general population.
Tuberculosis incidence among both adults with HIV and adults without HIV increased during 1998-2004 then remained relatively stable until 2007. During 2007-2012, tuberculosis incidence declined by 28-44% among adults with HIV and by 11-26% among adults without HIV, concurrent with an increase in antiretroviral therapy uptake. In 2012, tuberculosis incidence among adults with HIV (1,839-1,936 cases/100,000 population) was still eight times as high as among adults without HIV (231-238 cases/100,000 population), and approximately one third of tuberculosis cases were attributable to HIV.
Although tuberculosis incidence has declined among adults with and without HIV, the persistent high incidence of tuberculosis among those with HIV and the disparity between the two groups are concerning. Early diagnosis of HIV, early initiation of antiretroviral therapy, regular screening for tuberculosis, and isoniazid preventive therapy among persons with HIV, as well as tuberculosis control in the general population, are required to address these issues.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: Criterion-standard specimens for tuberculosis diagnosis in young children, gastric aspirate (GA) and induced sputum, are invasive and rarely collected in resource-limited settings. A far ...less invasive approach to tuberculosis diagnostic testing in children younger than 5 years as sensitive as current reference standards is important to identify. OBJECTIVE: To characterize the sensitivity of preferably minimally invasive specimen and assay combinations relative to maximum observed yield from all specimens and assays combined. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cross-sectional diagnostic study, the reference standard was a panel of up to 2 samples of each of 6 specimen types tested for Mycobacterium tuberculosis complex by Xpert MTB/RIF assay and mycobacteria growth indicator tube culture. Multiple different combinations of specimens and tests were evaluated as index tests. A consecutive series of children was recruited from inpatient and outpatient settings in Kisumu County, Kenya, between October 2013 and August 2015. Participants were children younger than 5 years who had symptoms of tuberculosis (unexplained cough, fever, malnutrition) and parenchymal abnormality on chest radiography or who had cervical lymphadenopathy. Children with 1 or more evaluable specimen for 4 or more primary study specimen types were included in the analysis. Data were analyzed from February 2015 to October 2020. MAIN OUTCOMES AND MEASURES: Cumulative and incremental diagnostic yield of combinations of specimen types and tests relative to the maximum observed yield. RESULTS: Of the 300 enrolled children, the median (interquartile range) age was 2.0 (1.0-3.6) years, and 151 (50.3%) were female. A total of 294 met criteria for analysis. Of 31 participants with confirmed tuberculosis (maximum observed yield), 24 (sensitivity, 77%; interdecile range, 68%-87%) had positive results on up to 2 GA samples and 20 (sensitivity, 64%; interdecile range, 53%-76%) had positive test results on up to 2 induced sputum samples. The yields of 2 nasopharyngeal aspirate (NPA) samples (23 of 31 sensitivity, 74%; interdecile range, 64%-84%), of 1 NPA sample and 1 stool sample (22 of 31 sensitivity, 71%; interdecile range, 60%-81%), or of 1 NPA sample and 1 urine sample (21.5 of 31 sensitivity, 69%; interdecile range, 58%-80%) were similar to reference-standard specimens. Combining up to 2 each of GA and NPA samples had an average yield of 90% (28 of 31). CONCLUSIONS AND RELEVANCE: NPA, in duplicate or in combination with stool or urine specimens, was readily obtainable and had diagnostic yield comparable with reference-standard specimens. This combination could improve tuberculosis diagnosis among children in resource-limited settings. Combining GA and NPA had greater yield than that of the current reference standards and may be useful in certain clinical and research settings.
While the number of reported tuberculosis (TB) cases in the United States has declined over the past two decades, TB morbidity among foreign-born persons has remained persistently elevated. A recent ...unexpected decline in reported TB cases among foreign-born persons beginning in 2007 provided an opportunity to examine contributing factors and inform future TB control strategies. We investigated the relative influence of three factors on the decline: 1) changes in the size of the foreign-born population through immigration and emigration, 2) changes in distribution of country of origin among foreign-born persons, and 3) changes in the TB case rates among foreign-born subpopulations. Using data from the U.S. National Tuberculosis Surveillance System and the American Community Survey, we examined TB case counts, TB case rates, and population estimates, stratified by years since U.S. entry and country of origin. Regression modeling was used to assess statistically significant changes in trend. Among foreign-born recent entrants (<3 years since U.S. entry), we found a 39.5% decline (-1,013 cases) beginning in 2007 (P<0.05 compared to 2000-2007) and ending in 2011 (P<0.05 compared to 2011-2014). Among recent entrants from Mexico, 80.7% of the decline was attributable to a decrease in population, while the declines among recent entrants from the Philippines, India, Vietnam, and China were almost exclusively (95.5%-100%) the result of decreases in TB case rates. Among foreign-born non-recent entrants (≥3 years since U.S. entry), we found an 8.9% decline (-443 cases) that resulted entirely (100%) from a decrease in the TB case rate. Both recent and non-recent entrants contributed to the decline in TB cases; factors contributing to the decline among recent entrants varied by country of origin. Strategies that impact both recent and non-recent entrants (e.g., investment in overseas TB control) as well as those that focus on non-recent entrants (e.g., expanded targeted testing of high-risk subgroups among non-recent entrants) will be necessary to achieve further declines in TB morbidity among foreign-born persons.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purfield reports that high-quality parasitic disease laboratory services are a priority at the CDC. The CDC is unwavering in their commitment to provide the highest quality laboratory diagnostic ...services for parasitic diseases. They clearly hear, understand, and concur with the concerns expressed in the accompanying editorial and appreciate the challenges the pause in testing for parasitic diseases presents for health-care providers, particularly those treating people at elevated risk for parasitic diseases. The CDC's laboratories must meet and maintain the highest standards of excellence to serve as the nation's premier health protection agency and to maintain the confidence of our citizens, public health experts, and clinical partners. We are working diligently to implement laboratory improvements to ensure we can meet these expectations and continue offering high-quality diagnostic services. Unfortunately, achievement of these improvements has required temporary suspension of some services.
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