Niclas Winqvist

Intensified Tuberculosis Case-Finding in HIV-Positive Adults Managed at Ethiopian Health Centers: Diagnostic Yield of Xpert MTB/RIF Compared with Smear Microscopy and Liquid Culture

Background Detection of active tuberculosis (TB) before antiretroviral therapy (ART) initiation is important, but optimal diagnostic methods for use in resource-limited settings are lacking. We assessed the prevalence of TB, evaluated the diagnostic yield of Xpert MTB/RIF in comparison with smear microscopy and culture, and the impact of Xpert results on clinical management in HIV-positive adults eligible for ART at health centers in a region of Ethiopia. Methods Participants were prospectively recruited and followed up at 5 health centers. Trained nurses collected data on socio-demographic characteristics, medical history and symptoms, and performed physical examination. Two paired morning sputum samples were obtained, and lymph node aspirates in case of lymphadenopathy. Diagnostic yield of Xpert MTB/RIF in sputum was compared with smear microscopy and liquid culture. Results TB was diagnosed in 145/812 participants (17.9%), with bacteriological confirmation in 137 (16.9%). Among bacteriologically confirmed cases, 31 were smear-positive (22.6%), 96 were Xpert-positive (70.1%), and 123 were culture-positive (89.8%). Xpert MTB/RIF increased the TB detection rate by 64 cases (47.4%) compared with smear microscopy. The overall sensitivity of Xpert MTB/RIF was 66.4%, and was not significantly lower when testing one compared with two samples. While Xpert MTB/RIF was 46.7% sensitive among patients with CD4 cell counts >200 cells/mm3, this increased to 82.9% in those with CD4 cell counts ≤100 cells/mm3. Compared with Xpert-positive TB patients, Xpert-negative cases had less advanced HIV and TB disease characteristics. Conclusions Previously undiagnosed TB is common among HIV-positive individuals managed in Ethiopian health centers. Xpert MTB/RIF increased TB case detection, especially in patients with advanced immunosuppression. An algorithm based on the use of a single morning sputum sample for individuals with negative sputum smear microscopy could be considered for intensified case finding in patients eligible for ART. However, technical and cost-effectiveness issues relevant for low-income countries warrant further study.

A case‐control study of transmission routes for GB virus C/hepatitis G virus in Swedish blood donors lacking markers for hepatitis C virus infection

The transmission routes for GB virus‐C (GBV‐C)/hepatitis G virus (HGV) in blood donors unexposed to hepatitis C virus (HCV) are unknown. We performed a case‐control study of risk factors for GBV‐C/HGV exposure in blood donors.

Use of a T cell interferon gamma release assay in the investigation for suspected active tuberculosis in a low prevalence area

BackgroundIn settings with low background prevalence of tuberculosis (TB) infection, interferon-γ release assays (IGRA) could be useful for diagnosing active TB. This study aims to evaluate the performance of QuantiFERON®-TB Gold (QFT-G) in the investigation for suspected active TB, with particular attention to patients originating in high-incidence countries. Furthermore, factors associated with QFT-G results in patients with active TB were assessed.MethodsFrom patients investigated for clinically suspected active TB, blood was obtained for QFT-G testing, in addition to routine investigations. Positive (PPV) and negative (NPV) predictive values for QFT-G were calculated, comparing patients with confirmed TB and those with other final diagnoses. QFT-G results in TB patients originating from countries with intermediate or high TB incidence were compared with QFT-G results from a control group of recently arrived asymptomatic immigrants from high-incidence countries. Factors associated with QFT-G outcome in patients with confirmed TB were assessed.ResultsAmong 141 patients, 41/70 (58.6%) with confirmed TB had a positive QFT-G test, compared to 16/71 (22.6%) patients with other final diagnoses, resulting in overall PPV of 71.9% and NPV of 67.6%. For patients with pulmonary disease, PPV and NPV were 61.1% and 67.7%, respectively, and 90.5% and 66.7% for subjects with extrapulmonary manifestations. Comparing patients from high-incidence countries with controls yielded a PPV for active TB of 76.7%, and a NPV of 82.7%. Patients with confirmed TB and positive QFT-G results were characterized by a lower median peripheral white blood cell count (5.9 × 109/L vs. 8.8 × 109/L; P < 0.001) and a higher median body mass index (22.7 vs. 20.7; P = 0.043) as compared to QFT-G-negative TB patients.ConclusionThe overall PPV and NPV of QFT-G for identifying active TB were unsatisfactory, especially for pulmonary disease. Thus, the usefulness of QFT-G for this purpose is questionable. However, a high PPV was observed for extrapulmonary TB and QFT-G might be considered in the diagnostic process in this situation. The PPV and NPV for identifying active TB among persons originating from regions with high-and intermediate TB incidence was similar to that observed in subjects originating in the low-incidence region.

Detection of lipoarabinomannan in urine for identification of active tuberculosis among HIV-positive adults in Ethiopian health centres

To assess the diagnostic performance of urine lipoarabinomannan (LAM) detection for TB screening in HIV‐positive adults in Ethiopia.

Long-term course of Mycobacterium tuberculosis infection in Swedish birth cohorts during the twentieth century.

SETTING Sweden under transition from high to low tuberculosis (TB) incidence from 1920 to 2009. OBJECTIVE To correlate estimates of TB infection in birth cohorts with the longitudinal incidence of active TB to assess the long-term risk and time pattern of reactivated TB. DESIGN Time trend analysis on TB incidence using age-cohort modelling. RESULTS The overall TB incidence decreased from 700 per 100,000 population in 1920 to 1.4 in 2009 in the Sweden-born population. The estimated disease rate (number of cases divided by the estimated number of infected in 1967), for each birth cohort between 1920 and 1940, was stable on a level between 9.8% and 10.7%. The reactivation rate of latent TB infection (LTBI) was 2% after 1967, when indigenous transmission had disappeared. CONCLUSION Although approximately 10% of persons with LTBI developed active TB, the majority of cases occurred shortly after infection, and the rates of reactivation declined over time. This indicates extensive spontaneous clearance of LTBI.

Outcome of tuberculosis treatment in HIV-positive adults diagnosed through active versus passive case-finding.

Background The World Health Organization strongly recommends regular screening for tuberculosis (TB) in HIV-positive individuals. Objective To compare the outcome of anti-tuberculosis treatment (ATT) in HIV-positive adults diagnosed with TB through active case-finding (ACF) or passive case-finding (PCF). Design Antiretroviral therapy (ART)-naïve adults diagnosed with TB were included from two prospective cohort studies conducted in Ethiopia between September 2010 and March 2013. The PCF cohort was based at out-patient TB clinics, whereas participants in the ACF cohort were actively screened for TB by bacteriological sputum testing (smear microscopy, Xpert MTB/RIF assay, and liquid culture) without pre-selection on the basis of symptoms and signs. Outcomes of ATT were compared between participants in the two cohorts; characteristics at diagnosis and predictors of adverse outcomes were analysed. Results Among 439 TB/HIV co-infected participants, 307 and 132 belonged to PCF and ACF cohorts, respectively. Compared with the ACF participants, hemoptysis, conjunctival pallor, bedridden status, and low mid upper-arm circumference (MUAC) were significantly more common in participants identified through PCF. Sputum smear-positivity rates among pulmonary TB cases were 44.2% and 21.1% in the PCF and ACF cohorts, respectively (p<0.001). Treatment success was ascertained in 247 (80.5%) of the participants in the PCF cohort and 102 (77.2%) of the participants in the ACF cohorts (p=0.223). Low MUAC (p=0.001) independently predicted mortality in the participants in both cohorts. Conclusion Although patients identified through ACF had less advanced TB disease, ATT outcome was similar to the patients identified through PCF. To achieve a better outcome, case management in ACF strategy should be strengthened through enhanced patient-centred counselling and adherence support.Background The World Health Organization strongly recommends regular screening for tuberculosis (TB) in HIV-positive individuals. Objective To compare the outcome of anti-tuberculosis treatment (ATT) in HIV-positive adults diagnosed with TB through active case-finding (ACF) or passive case-finding (PCF). Design Antiretroviral therapy (ART)-naïve adults diagnosed with TB were included from two prospective cohort studies conducted in Ethiopia between September 2010 and March 2013. The PCF cohort was based at out-patient TB clinics, whereas participants in the ACF cohort were actively screened for TB by bacteriological sputum testing (smear microscopy, Xpert MTB/RIF assay, and liquid culture) without pre-selection on the basis of symptoms and signs. Outcomes of ATT were compared between participants in the two cohorts; characteristics at diagnosis and predictors of adverse outcomes were analysed. Results Among 439 TB/HIV co-infected participants, 307 and 132 belonged to PCF and ACF cohorts, respectively. Compared with the ACF participants, hemoptysis, conjunctival pallor, bedridden status, and low mid upper-arm circumference (MUAC) were significantly more common in participants identified through PCF. Sputum smear-positivity rates among pulmonary TB cases were 44.2% and 21.1% in the PCF and ACF cohorts, respectively (p<0.001). Treatment success was ascertained in 247 (80.5%) of the participants in the PCF cohort and 102 (77.2%) of the participants in the ACF cohorts (p=0.223). Low MUAC (p=0.001) independently predicted mortality in the participants in both cohorts. Conclusion Although patients identified through ACF had less advanced TB disease, ATT outcome was similar to the patients identified through PCF. To achieve a better outcome, case management in ACF strategy should be strengthened through enhanced patient-centred counselling and adherence support.

A Clinical Scoring Algorithm for Determination of the Risk of Tuberculosis in HIV-Infected Adults: A Cohort Study Performed at Ethiopian Health Centers

Among HIV-infected, antiretroviral therapy (ART)–naive adults with positive World Health Organization tuberculosis (TB) symptom screening, clinical scoring could categorize patients for the risk of TB. This strategy would reduce the proportion of patients requiring TB testing before starting ART.

Demographics of tuberculosis in an emerging EU region in Southern Scandinavia

To describe demographics of tuberculosis (TB) in the Øresund region, southern Scandinavia, a retrospective analysis of epidemiological data from TB registers and population databases, from 1995 to 2002, was performed. A total of 2678 TB cases were reported with an overall incidence of 6.3 per 100,000 person-y of observation. There were major differences in notification rates among immigrants depending on their country of origin and their residence in the Øresund region. In the Danish part, 37% of all cases among immigrants came from the Horn of Africa compared to 28% in the Swedish areas. Older age and residence in Denmark were independent risk factors for TB. Comparisons of TB rates within the group of immigrants from the Horn of Africa showed higher rates in the Danish areas compared to the Swedish areas. The discrepancies in notification rates could be explained by different socioeconomic circumstances in the 2 countries or by a greater immigration from highly endemic countries into Denmark during the study period; however, ongoing transmission in specific population groups at high risk of tuberculosis cannot be excluded. This highlights the need for continued and improved surveillance for TB, especially among newly arrived immigrants from highly endemic countries.

Impaired pulmonary function and the risk of tuberculosis: a population-based cohort study

To the Editors: It is well known that pulmonary tuberculosis (TB) can cause lung impairment leading to chronic obstructive pulmonary disease (COPD) 1, but less is known to what extent impaired lung function increases the risk of TB. A case–control study from the UK found patients with emphysema to have a three-fold increased risk of TB, adjusted for smoking and the use of corticosteroids 2. A cohort study from Denmark found moderate-to-severe COPD to be associated with a two- to three-fold increased risk of hospitalisation with TB 3. We have previously shown that patients hospitalised with COPD have a three-fold increased risk of active TB compared with population controls 4. In the present study, we examine the risk of active TB in relation to lung function in a cohort who underwent spirometry in 1974–1992. Between 1974 and 1992, 22,444 males and 10,902 females, born 1921–1949, participated in a health screening programme, the Malmo Preventive Project. Complete birth cohorts, born in pre-specified years, from the city of Malmo were invited; the overall participation proportion was ∼70% 5. The screening included physical examination, spirometry, blood samples and assessment of lifestyle factors by means of a self-administered questionnaire. Some questions varied between the cohorts. We excluded 4,413 individuals because of missing spirometry data; 26 individuals were excluded because of missing data on either body mass index (BMI), smoking or immigration status, leaving a total of 28,907 individuals in final analysis (21,174 males and 7,733 females). BMI as was calculated as mass/height2 (in kg·m−2). Individuals were regarded as having diabetes mellitus if they answered positively to the question “Do you have diabetes mellitus?” or their fasting blood glucose level was ≥6.1 mmol·L−1. Around 96% of the cohort (n = 27,789) answered questions on alcohol. Individuals …

Performance of QuantiFERON-TB Gold Plus for detection of latent tuberculosis infection in pregnant women living in a tuberculosis- and HIV-endemic setting

We evaluated the performance of QuantiFERON-TB Gold Plus (QFT-Plus), which includes two Mycobacterium tuberculosis antigen formulations (TB1 and TB2), for detection of latent tuberculosis infection during pregnancy. Eight-hundred-twenty-nine Ethiopian pregnant women (5.9% HIV-positive) were tested with QFT-Plus, with bacteriological sputum analysis performed for women with clinically suspected tuberculosis and HIV-positive women irrespective of clinical presentation. QFT-Plus read-out was categorized according to the conventional cut-off (0.35 IU/ml) for both antigen formulations. In addition, we analysed the distribution of QFT-Plus results within a borderline zone (0.20–0.70 IU/ml), and interferon-γ response in relation to HIV infection and gestational age. Two-hundred-seventy-seven women (33%) were QFT-Plus-positive (HIV-positive 16/49 [33%]; HIV-negative 261/780 [33%]). There was a strong agreement between the two antigen formulations (κ = 0.92), with discordant results in 29 cases (3.5%). Whereas discordant QFT-Plus results were rare in pregnancy, several results with both TB1 and TB2 within the borderline range were observed (11/49 [22%] vs. 43/780 [5.5%] in HIV-positive and HIV-negative women, respectively; p<0.0001). HIV-positive women had lower absolute interferon-γ levels (TB1: 0.47 vs. 2.16 IU/ml; p<0.001, TB2: 0.49 vs. 2.24 IU/ml, p<0.001, considering results ≥0.20 IU/ml) compared to HIV-negative women. QFT-Plus-positive women who submitted samples at later stages of pregnancy had lower mitogen- (p<0.001) but higher TB-antigen-specific (p = 0.031 for TB1, p = 0.061 for TB2) interferon-γ response. Considering their lower capacity to produce TB-specific interferon-γ, a lower cut-off level for defining QFT-Plus-positivity may be considered in HIV-positive pregnant women.