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Aims: The aim of this paper is to explore experiences of being diagnosed with tuberculosis (TB) among immigrants in Norway, with a view to factors associated with diagnostic delay. Methods: A qualitative study was conducted among 22 participants diagnosed with TB who originated from Somalia or Ethiopia. Results: One-third of the participants reported less than 2 months from onset of symptoms to treatment were initiated. The factors associated with little delay included a medical history that gave suspicion of TB, presenting with typical TB symptoms, or being screened for TB at arrival. Two-thirds of the participants told about extensive diagnostic processes. Persistent cough not accompanied by symptoms such as: weight loss and weakness; mild, diffuse, atypical, and/or intermittent symptoms; and a sense of not being a likely victim of TB could delay patients' first initiative to seek help. Participants experienced that the diagnostic process in the health services could endure for months, even years. The diagnosis could be difficult to confirm, but health professionals appeared to have difficulties with associating their symptoms with TB. This resulted in delays in initiating diagnostic tests for TB, especially in cases of extra-pulmonary TB. Conclusions: Public health efforts to increase awareness about TB transmission, its diversity in manifestations, and its progression from latent to active disease, may decrease patient delay. An increased awareness among health professionals about typical and atypical symptoms of TB, aspects of the patient's history, and being aware and sensitive to patients' own interpretation of symptoms may reduce diagnostic delay in the health services. [ABSTRACT FROM AUTHOR]

Background: The health system of Sudan has experienced several forms of decentralization, as well as, a radical reform. Authority and governance of secondary and tertiary health facilities have been shifted from federal to state levels. Moreover, the provision of health care services have been moved from large federal tertiary level hospitals such as Khartoum Teaching Hospital (KTH) and Jafaar Ibnoaf Hospital (JIH), located in the center of Khartoum, to smaller district secondary hospitals like Ibrahim Malik (IBMH), which is located in the southern part of Khartoum. Exploring stakeholders' perceptions on this decentralisation implementation and its relevant consequences is vital in building an empirical benchmark for the improvement of health systems., Methods: This study utilised a qualitative design which is comprised of in-depth interviews and qualitative content analysis with an inductive approach. The study was conducted between July and December 2015, and aimed at understanding the personal experiences and perceptions of stakeholders towards decentralisation enforcement and the implications on public health services, with a particular focus on the Khartoum locality. It involved community members residing in the Khartoum Locality, specifically in catchments area where hospital decentralisation was implemented, as well as, affiliated health workers and policymakers., Results: The major finding suggested that privatisation of health services occurred after decentralisation. The study participants also highlighted that scrutiny and reduction of budgets allocated to health services led to an instantaneous enforcement of cost recovery user fee. Devolving KTH Khartoum Teaching and Jafar Ibnoaf Hospitals into peripherals with less. Capacity, was considered to be a plan to weaken public health services and outsource services to private sector. Another theme that was highlighted in hospitals included the profit-making aspect of the governmental sector in the form of drug supplying and profit-making retail., Conclusions: A change in health services after the enforcement of decentralisation was illustrated. Moreover, the incapacitation of public health systems and empowerment of the privatisation concept was the prevailing perception among stakeholders. Having contextualised in-depth studies and policy analysis in line with the global liberalisation and adjustment programmes is crucial for any health sector reform in Sudan.

Understanding mechanisms of cavitation in tuberculosis (TB) is the missing link that could advance the field towards better control of the infection. Descriptions of human TB suggest that postprimary TB begins as lipid pneumonia of foamy macrophages that undergoes caseating necrosis and fragmentation to produce cavities. This study aimed to investigate the various mycobacterial antigens accumulating in foamy macrophages and their relation to tissue destruction and necrosis. Pulmonary tissues from mice with slowly progressive TB were studied for histopathology, acid-fast bacilli (AFB) and presence of mycobacterial antigens. Digital quantification using Aperio ImageScope was done. Until week 12 postinfection, mice were healthy, and lesions were small with scarce AFB and mycobacterial antigens. Colony-forming units (CFUs) increased exponentially. At week 16-33, mice were sick, macrophages attained foamy appearance with an increase in antigens (P < .05), 1.5 log increase in CFUs and an approximately onefold increase in AFB. At week 37-41, mice started dying with a shift in morphology towards necrosis. A >20-fold increase in mycobacterial antigens was observed with only less than one log increase in CFUs and sevenfold increase in AFB. Secreted antigens were significantly (P < .05) higher compared to cell-wall antigens throughout infection. Focal areas of necrosis were associated with an approximately 40-fold increase in antigen MPT46, functionally active thioredoxin, and a significant increase in all secreted antigens. In conclusion, mycobacterial antigens accumulate in the foamy macrophages in TB lesions during slowly progressive murine pulmonary TB. Secreted antigens and MPT46 correlated with necrosis, thereby implying that they might trigger the formation of cavities., (© 2020 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.)

Objective: The recent 2014 Ebola Virus Disease (EVD) outbreaks rang the bell to call upon global efforts to assist resource-constrained countries to strengthen public health surveillance system for early response. Malawi adopted the Integrated Disease Surveillance and Response (IDSR) strategy to develop its national surveillance system since 2002 and revised its guideline to fulfill the International Health Regulation (IHR) requirements in 2014. This study aimed to understand the state of IDSR implementation and differences between guideline and practice for future disease surveillance system strengthening., Methods: This was a mixed-method research study. Quantitative data were to analyze completeness and timeliness of surveillance system performance from national District Health Information System 2 (DHIS2) during October 2014 to September 2016. Qualitative data were collected through interviews with 29 frontline health service providers from the selected district and 7 key informants of the IDSR system implementation and administration at district and national levels., Findings: The current IDSR system showed relatively good completeness (73.1%) but poor timeliness (40.2%) of total expected monthly reports nationwide and zero weekly reports during the study period. Major implementation gaps were lack of weekly report and trainings. The challenges of IDSR implementation revealed through qualitative data included case identification, compiling reports for timely submission and inadequate resources., Conclusions: The differences between IDSR technical guideline and actual practice were huge. The developing information technology infrastructure in Malawi and emerging mobile health (mHealth) technology can be opportunities for the country to overcome these challenges and improve surveillance system to have better timeliness for the outbreaks and unusual events detection., Competing Interests: The authors have declared that no competing interests exist.

Background: Measuring the size of the infectious pool of tuberculosis (TB) is essential to understand the burden and monitor trends of TB control program performance. This study applied the concept of TB management time to estimate and compare the size of the TB infectious pool between 2009 and 2014 in West Gojjam Zone of Amhara Region, Ethiopia., Methods: New sputum smear-positive and smear-negative pulmonary TB (PTB) and retreatment cases who attended 30 randomly selected public health facilities in West Gojjam Zone from October 2013 to October 2014 were consecutively enrolled in the study. In order to determine the infectious period, the TB management time (number of days from the onset of cough until start of anti-TB treatment) was computed for each patient category. The number of undiagnosed TB cases was estimated and hence the TB management time for the undiagnosed category was calculated. The total size of the TB infectious pool during the study period for the study zone was estimated as the annual number of infectious person days., Results: New smear-positive and smear-negative PTB cases contributed 25,050 and 12,931 infectious person days per year to the TB infectious pool, respectively. The retreatment and presently undiagnosed cases contributed 8840 and 34,310 infectious person days per year, respectively. The total size of the TB infectious pool in West Gojjam Zone during the study period was estimated at 81,131 infectious person days per year or 3405 infectious person days per 100,000 population per year. Compared to a similar study done in 2009 in the study area, the current study showed reduction of the TB infectious pool by 244,279 infectious person days., Conclusions: TB management time is a simple and practical tool that may help to estimate and compare the changes in the size of the TB infectious pool at local level. It may also be used as an indicator to monitor the changes in TB control program performance.

Introduction: The dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a major global public health concern. There is mounting evidence from different countries on the burden of TB and DM comorbidity. The objective of this systematic review was to summarize the existing evidence on prevalence and associated/risk factors of TBDM comorbidity at global and regional levels., Methods: Ovid Medline, Embase, Global health, Cochrane library, Web of science and Scopus Elsevier databases were searched to identify eligible articles for the systematic review. Data were extracted using standardized excel form and pilot tested. Median with interquartile range (IQR) was used to estimate prevalence of TBDM comorbidity. Associated/risk factors that were identified from individual studies were thematically analyzed and described., Results: The prevalence of DM among TB patients ranged from 1.9% to 45%. The overall median global prevalence was 16% (IQR 9.0%-25.3%) Similarly, the prevalence of TB among DM patients ranged from 0.38% to 14% and the overall median global prevalence was 4.1% (IQR 1.8%-6.2%). The highest prevalence of DM among TB patients is observed in the studied countries of Asia, North America and Oceania. On the contrary, the prevalence of TB among DM patients is low globally, but relatively higher in the studied countries of Asia and the African continents. Sex, older age, urban residence, tobacco smoking, sedentary lifestyle, poor glycemic control, having family history of DM and TB illness were among the variables identified as associated/risk factors for TBDM comorbidity., Conclusion: This systematic review revealed that there is a high burden of DM among TB patients at global level. On the contrary, the global prevalence of TB among DM patients is low. Assessing the magnitude and risk/associated factors of TBDM comorbidity at country/local level is crucial before making decisions to undertake TBDM integrated services.

Background: Tuberculosis (TB) is a major public health concern in the developing world. Early diagnosis and prompt initiation of treatment is essential for effective TB control. The aim of this study was to determine the length and analyze associated factors of patients' and health system's delays in the diagnosis and treatment of new pulmonary TB (PTB) patients., Methods: A cross-sectional study was conducted in 30 randomly selected public health facilities in West Gojjam Zone, Amhara Region, Ethiopia. Newly diagnosed PTB patients who were ≥15 years of age were consecutively enrolled in the study. Patients' delay (the time period from onset of TB symptoms to first presentation to a formal health provider) and health system's delay (the time period from first presentation to a formal health provider to first start of TB treatment) were measured. Median patients' and health system's delays were calculated. Mixed effect logistic regression was used to analyze predictors of patients' and health system's delays., Results: Seven hundred six patients were enrolled in the study. The median patients' delay was 18 days (interquartile range [IQR]: 8-34 days) and the median health system's delay was 22 days (IQR: 4-88 days). Poor knowledge of TB (adjusted odds ratio [AOR], 2.33; 95 % confidence interval [CI], 1.34-4.05), first visit to non-formal health provider (AOR, 47.56; 95 % CI, 26.31-85.99), self-treatment (AOR, 10.11; 95 % CI, 4.53-22.56) and patients' age (≥45 years) (AOR, 2.99; 95 % CI, 1.14-7.81) were independent predictors of patients' delay. Smear-negative TB (AOR, 1.88; 95 % CI, 1.32-2.68) and first visit to public health centers (AOR, 2.22; 95 % CI, 1.52-3.25) and health posts (AOR, 5.86; 95 % CI, 1.40-24.39) were found to be independent predictors of health system's delay., Conclusions: The health system's delay in this study was long and contributed more than 50 % of the total delay. Better TB diagnostic tools to complement sputum smear microscopy are needed to early diagnose PTB cases at peripheral health facilities. In addition, due emphasis should be given to increase public awareness about symptoms and consequences of TB disease.

Background: delay in diagnosis and treatment of tuberculosis (TB) may worsen the disease, increase mortality and enhance transmission in the community. This study aimed at assessing the association between total delay and unfavorable treatment outcome among newly diagnosed pulmonary TB (PTB) patients., Methods: A prospective cohort study was conducted in West Gojjam Zone, Amhara Region of Ethiopia from October 2013 to May 2015. Newly diagnosed PTB patients who were ≥15 years of age were consecutively enrolled in the study from 30 randomly selected public health facilities. Total delay (the time period from onset of TB symptoms to first start of anti-TB treatment) was measured. Median total delay was calculated. Mixed effect logistics regression was used to analyze factors associated with unfavorable treatment outcome., Results: Seven hundred six patients were enrolled in the study. The median total delay was 60 days. Patients with total delay of > 60 days were more likely to have unfavorable TB treatment outcome than patients with total delay of ≤ 60 days (adjusted odds ratio [AOR], 2.33; 95% confidence interval [CI], 1.04-5.26). Human immunodeficiency virus (HIV) positive TB patients were 8.46 times more likely to experience unfavorable treatment outcome than HIV negative TB patients (AOR, 8.46; 95% CI, 3.14-22.79)., Conclusions: Long total delay and TB/HIV coinfection were associated with unfavorable treatment outcome. Targeted interventions that can reduce delay in diagnosis and treatment of TB, and early comprehensive management of TB/HIV coinfection are needed to reduce increased risk of unfavorable treatment outcome.

Background: The double burden of tuberculosis (TB) and diabetes mellitus (DM) is a significant public health problem in low and middle income countries. However, despite the known synergy between the two disease conditions, services for TB and DM have separately been provided. The objective of this study was to explore health system challenges and opportunities for possible integration of DM and TB services., Methods: This was a descriptive qualitative study which was conducted in South-Eastern Amhara Region, Ethiopia. Study participants included health workers (HWs), program managers and other stakeholders involved in TB and DM prevention and control activities. Purposive sampling was applied to select respondents. In order to capture diversity of opinions among participants, maximum variation sampling strategy was applied in the recruitment of study subjects. Data were collected by conducting four focus group discussions and 12 in-depth interviews. Collected data were transcribed verbatim and were thematically analyzed using NVivo 10 software program., Result: A total of 44 (12 in-depth interviews and 32 focus group discussion) participants were included in the study. The study participants identified a number of health system challenges and opportunities affecting the integration of TB-DM services. The main themes identified were: 1. Unavailability of system for continuity of DM care. 2. Inadequate knowledge and skills of health workers. 3. Frequent stockouts of DM supplies. 4. Patient's inability to pay for DM services. 5. Poor DM data management. 6. Less attention given to DM care. 7. Presence of a well-established TB control program up to the community level. 8. High level of interest and readiness among HWs, program managers and leaders at different levels of the health care delivery system., Conclusion: The study provided insights into potential health systems challenges and opportunities that need to be considered in the integration of TB-DM services. Piloting TB and DM integrated services in selected HFs of the study area is needed to assess feasibility for possible full scale integration of services for the two comorbid conditions.

Background: There is growing evidence suggesting that diabetes mellitus (DM) affects disease presentation and treatment outcome in tuberculosis (TB) patients. This study aimed at investigating the role of DM on clinical presentations and treatment outcomes among newly diagnosed TB patients., Methods: A prospective cohort study was conducted in South-Eastern Amhara Region, Ethiopia from September 2013 till March 2015. Study subjects were consecutively recruited from 44 randomly selected health facilities in the study area. Participants were categorized into two patient groups, namely, patients with TB and DM (TBDM) and TB patients without DM (TBNDM). Findings on clinical presentations and treatment outcomes were compared between the two patient groups. Cox proportional hazard regression analysis was applied to identify factors associated with death., Results: Out of 1314 TB patients enrolled in the study, 109 (8.3 %) had coexisting DM. TBDM comorbidity [adjusted hazard ratio (AHR) 3.96; 95 % confidence interval (C.I.) (1.76-8.89)], and TB coinfection with human immunodeficiency virus (HIV) [AHR 2.59; 95 % C.I. (1.21-5.59)] were associated with increased death. TBDM and TBNDM patients did not show significant difference in clinical symptoms at baseline and during anti-TB treatment period. However, at the 2(nd) month of treatment, TBDM patients were more symptomatic compared to patients in the TBNDM group., Conclusions: The study showed that DM is associated with increased death during TB treatment. DM has no association with clinical presentation of TB except at the end of the intensive phase treatment. Routine screening of TB patients for DM is recommended for early diagnosis and treatment of patients with TBDM comorbidity.

Background: The association between diabetes mellitus (DM) and tuberculosis (TB) is re-emerging worldwide. Recently, the prevalence of DM is increasing in resource poor countries where TB is of high burden. The objective of the current study was to determine the prevalence and analyze associated factors of TB and DM comorbidity in South-Eastern Amhara Region, Ethiopia., Methods: This was a facility based cross-sectional study. All newly diagnosed TB patients attending selected health facilities in the study area were consecutively screened for DM. DM was diagnosed based on the World Health Organization diagnostic criteria. A pre-tested semi-structured questionnaire was used to collect socio-demographic, lifestyles and clinical data. Logistic regression analysis was performed to identify factors associated with TB and DM comorbidity., Result: Among a total of 1314 patients who participated in the study, the prevalence of DM was estimated at 109 (8.3%). Being female [odds ratio (OR) 1.70; 95% confidence interval (CI) (1.10-2.62)], patients age [41-64 years (OR 3.35; 95% CI (2.01-5.57), 65-89 years (OR 3.18; 95% CI (1.52-6.64)], being a pulmonary TB case [(OR 1.69; 95% CI 1.09-2.63)] and having a family history of DM [(OR 4.54; 95% CI (2.36-8.73)] were associated factors identified with TB and DM comorbidity., Conclusion: The prevalence of DM among TB patients in South-Eastern Amahra Region is high. Routine screening of TB patients for DM is recommended in the study area.

Background. Weak health systems pose many barriers to effective tuberculosis (TB) control. This study aimed at exploring health worker's and TB control program coordinator's perspectives on health systems challenges facing TB control in West Gojjam Zone, Amhara Region, Ethiopia. Methods. This was a qualitative descriptive study. Eight in-depth interviews with TB control program coordinators and two focus group discussions among 16 health workers were conducted. Purposive sampling was used to recruit study participants. Thematic analysis was used to identify and analyse main themes. Results. We found that intermittent interruptions of laboratory reagents and anti-TB drugs supplies, absence of trained and motivated health workers, poor TB data documentation, lack of adherence to TB treatment guideline, and lack of access to TB diagnostic tools at peripheral health institutions were challenges facing the TB control program performance in the study zone. Conclusions. Ensuring uninterrupted supply of anti-TB drugs and laboratory reagents to all health institutions is essential. Continuous refresher training of health workers on standard TB care and data handling and developing and implementing a sound retention strategy to attract and motivate health professionals to work in rural areas are necessary interventions to improve the TB control program performance in the study zone.

Background: The diagnosis of intestinal tuberculosis (ITB) is sometimes difficult to establish and requires endoscopic investigation with biopsies for histopathological examination. This study aimed to evaluate calprotectin as a marker of inflammation in ITB., Methods: Patients with ITB were prospectively recruited in Southern India from October 2009 until July 2012. Demographic, clinical, endoscopic and histological features were examined along with faecal calprotectin (FC), serum calprotectin (SC) and C-reactive protein (CRP)., Results: Thirty patients (median age 34.5 years, 19 men) were included. Clinical features were abdominal pain (97%), weight loss (83%), cachexia (75%), fatigue (63%), watery diarrhoea (62%), nausea (55%) and fever (53%). Endoscopy showed transverse ulcers (61%), nodularity of mucosa (55%), aphthous ulcers (39%), strictures (10%) and fissures (10%). The terminal ileum and right colon harboured 81% of the lesions. Histology revealed granulomas in biopsies from 10 of the patients. FC and CRP levels showed a strong positive correlation (rs = 0.70, p < 0.01). FC, SC and CRP levels were higher in the granulomatous than the non-granulomatous patients, respectively (median FC 988 μg/g, interquartile range (IQR) 940 vs 87 μg/g, IQR 704, p < 0.01; median SC 8.2 μg/ml, IQR 7.3 vs 3.8 μg/ml, IQR 8.9, p = 0.23; median CRP 38.8 mg/L, IQR 42.9 vs 2.3 mg/L, IQR 13.5, p < 0.01). Higher median calprotectin and CRP levels were detected in patients with extensive than localized disease, but the differences did not reach statistical significance., Conclusion: ITB patients with granulomas on histology have high levels of faecal calprotectin and CRP.

Background: Current methods to establish the diagnosis of intestinal tuberculosis are inadequate., Objectives: We aimed to determine the clinical features of intestinal tuberculosis and evaluate inflammatory biomarkers in intestinal as well as pulmonary tuberculosis., Methods: We recruited 38 intestinal tuberculosis patients, 119 pulmonary tuberculosis patients and 91 controls with functional gastrointestinal disorders between October 2009 and July 2012 for the investigation of clinical features, C-reactive protein (CRP), faecal and serum calprotectin. Faecal calprotectin ≥200 µg/g was used as a cut-off to determine intestinal inflammation of clinical significance. Three patient categories were established: (a) pulmonary tuberculosis and faecal calprotectin <200 µg/g (isolated pulmonary tuberculosis); (b) pulmonary tuberculosis and faecal calprotectin ≥200 µg/g (combined pulmonary and intestinal tuberculosis); (c) isolated intestinal tuberculosis., Results: Common clinical features of intestinal tuberculosis were abdominal pain, fatigue, weight loss and watery diarrhoea. Intestinal tuberculosis patients had elevated median CRP (10.7 mg/l), faecal calprotectin (320 µg/g) and serum calprotectin (5.7 µg/ml). Complete normalisation of CRP (1.0 mg/L), faecal calprotectin (16 µg/g) and serum calprotectin (1.4 µg/ml)) was seen upon clinical remission. Patients with combined pulmonary and intestinal tuberculosis had the highest levels of CRP (53.8 mg/l) and serum calprotectin (6.5 µg/ml) and presented with signs of more severe disease., Conclusion: Calprotectin analysis reveals intestinal tuberculosis in patients with pulmonary tuberculosis and pinpoints those in need of rigorous follow-up.

Setting: Delay in tuberculosis (TB) diagnosis increases the infectious pool in the community and the risk of development of resistance of mycobacteria, which results in an increased number of deaths., Objective: To describe patients' and doctors' perceptions of diagnostic delay in TB patients in the Arkhangelsk region and to develop a substantive model to better understand the mechanisms of how these delays are linked to each other., Design: A grounded theory approach was used to study the phenomenon of diagnostic delay. Patients with TB diagnostic delay and doctors-phthisiatricians were interviewed., Results: A model named 'sickness trajectory in health-seeking behaviour among tuberculosis patients' was developed and included two core categories describing two vicious circles of diagnostic delay in patients with TB: 'limited awareness of the importance to contact the health system' and 'limited resources of the health system' and the categories: 'factors influencing health-seeking behaviour' and 'factors influencing the health system effectiveness'. Men were more likely to report patient delay, while women were more likely to report health system delay., Conclusions: To involve people in early medical examinations, it is necessary to increase alertness on TB among patients and to improve health systems in the districts.

Aim: To investigate whether routinely measured clinical variables could aid in differentiating intestinal tuberculosis (ITB) from Crohn's disease (CD)., Methods: ITB and CD patients were prospectively included at four South Indian medical centres from October 2009 to July 2012. Routine investigations included case history, physical examination, blood biochemistry, ileocolonoscopy and histopathological examination of biopsies. Patients were followed-up after 2 and 6 mo of treatment. The diagnosis of ITB or CD was re-evaluated after 2 mo of antituberculous chemotherapy or immune suppressive therapy respectively, based on improvement in signs, symptoms and laboratory variables. This study was considered to be an exploratory analysis. Clinical, endoscopic and histopathological features recorded at the time of inclusion were subject to univariate analyses. Disease variables with sufficient number of recordings and P < 0.05 were entered into logistic regression models, adjusted for known confounders. Finally, we calculated the odds ratios with respective confidence intervals for variables associated with either ITB or CD., Results: This study included 38 ITB and 37 CD patients. Overall, ITB patients had the lowest body mass index (19.6 vs 22.7, P = 0.01) and more commonly reported weight loss (73% vs 38%, P < 0.01), watery diarrhoea (64% vs 33%, P = 0.01) and rural domicile (58% vs 35%, P < 0.05). Endoscopy typically showed mucosal nodularity (17/31 vs 2/37, P < 0.01) and histopathology more frequently showed granulomas (10/30 vs 2/35, P < 0.01). The CD patients more frequently reported malaise (87% vs 64%, P = 0.03), nausea (84% vs 56%, P = 0.01), pain in the right lower abdominal quadrant on examination (90% vs 54%, P < 0.01) and urban domicile (65% vs 42%, P < 0.05). In CD, endoscopy typically showed involvement of multiple intestinal segments (27/37 vs 9/31, P < 0.01). Using logistic regression analysis we found weight loss and nodularity of the mucosa were independently associated with ITB, with adjusted odds ratios of 8.6 (95%CI: 2.1-35.6) and 18.9 (95%CI: 3.5-102.8) respectively. Right lower abdominal quadrant pain on examination and involvement of ≥ 3 intestinal segments were independently associated with CD with adjusted odds ratios of 10.1 (95%CI: 2.0-51.3) and 5.9 (95%CI: 1.7-20.6), respectively., Conclusion: Weight loss and mucosal nodularity were associated with ITB. Abdominal pain and excessive intestinal involvement were associated with CD. ITB and CD were equally common.

Objective: To demonstrate the application of TB management time as an alternative parameter to estimate the size of the tuberculosis infectious pool in West Gojjam Zone of Amhara Region, Ethiopia., Methods: In this study, we used the TB management time, i.e. the number of days from start of cough until start of treatment, to determine the infectious period. Patients with sputum smear-positive and smear-negative pulmonary TB, retreatment and an estimated number of undetected cases were included. The infectious pool was then estimated as the annual number of infectious person days in a defined population., Results: The TB management time of presently undiagnosed TB cases and sputum smear-positive patients contributed significantly to the infectious pool with 151,840 and 128,750 infectious person days per year, respectively. The total infectious pool including sputum smear-negative TB cases and retreatment patients in the study area was estimated at 325,410 person days or 15,447 person days per 100,000 population during the study year., Conclusion: Recording TB management time may be used to estimate the infectious pool of TB and to monitor programme performance in the community., (© 2014 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Background: In Russia, active case finding (ACF) for certain population groups has been practiced uninterruptedly for many decades, but no studies comparing ACF and passive case finding (PCF) approaches in Russia have been published., Objective: The aim of this study was to describe the main differences in symptoms and diagnostic delay between patients who come to TB services through PCF and ACF strategies., Methods: A cross-sectional study was conducted among 453 new pulmonary tuberculosis (PTB) patients, who met criteria of TB diagnostic delay in Arkhangelsk., Results: ACF patients used self-treatment more often than PCF patients (90.1% vs. 24.6%) and 36.3% of them were alcohol abusers (as opposed to only 26.2% of PCF patients). The median patient delay (PD) in PCF was 4 weeks, IQR (1-8 weeks), and less than 1 week in ACF. Twenty-three per cent of the PCF patients were seen by a medical provider within the first week of their illness onset., Conclusion: Patients diagnosed through ACF tended to under-report their TB symptoms and showed low attention to their own health. However, ACF allowed for discovering TB patients earlier than PCF, and this was also the case for alcohol abusing patients. PCF systems should be supplemented with ACF strategies.

Background: Early detection and treatment of TB is essential for the success of TB control program performance. The aim of this study was to determine the length and analyze predictors of patients', health systems' and total delays among patients attending a referral hospital in Bahir Dar, Ethiopia., Methods: A cross-sectional study was conducted among newly diagnosed TB cases ≥ 15 years of age. Delay was analyzed at three levels: the periods between 1) onset of TB symptoms and first visit to medical provider, i.e. patients' delay, 2) the first visit to a medical provider and the initiation of treatment i.e. health systems' delay and 3) onset of TB symptoms and initiation of treatment i.e. total delay. Uni- and multi-variate logistic regression analyses were performed to investigate predictors of patients', health systems' and total delays., Results: The median time of patients' delay was 21 days [(interquartile range (IQR) (7 days, 60 days)]. The median health systems' delay was 27 days (IQR 8 days, 60 days) and the median total delay was 60 days (IQR 30 days, 121 days). Patients residing in rural areas had a three-fold increase in patients' delay compared to those from urban areas [Adjusted Odds Ratio (AOR) 3.4; 95% (CI 1.3, 8.9)]. Extra-pulmonary TB (EPTB) cases were more likely to experience delay in seeking treatment compared to pulmonary (PTB) cases [(AOR 2.6; 95% (CI 1.3, 5.4)]. Study subjects who first visited health centres [(AOR) 5.1; 95% (CI 2.1, 12.5)], private facilities [(AOR) 3.5; 95% (CI 1.3, 9.7] and health posts [(AOR) 109; 95% (CI 12, 958], were more likely to experience an increase in health systems' delay compared to those who visited hospitals., Conclusions: The majority of TB patients reported to medical providers within an acceptable time after the onset of symptoms. Rural residence was associated with patients' and total delays. Providing the population with information about TB symptoms and the importance of early health seeking may be an efficient way to decrease TB transmission, morbidity and mortality. Establishing efficient TB diagnostic and treatment facilities at the periphery level is imperative to reduce diagnostic delay and expedite TB treatment.

The aim of this study was to characterize Mycobacterium tuberculosis isolates circulating in the Amhara Region of Ethiopia. Sputum samples were collected from new pulmonary tuberculosis (TB) patients in the Region. Genotyping of mycobacterial DNA was performed by spoligotyping and isolates were assigned to families using the SpolDB4 and the model-based program 'Spotclust'. A high level of diversity was found among the 237 isolates. Sixty-five different spoligopatterns were obtained. The T (30.8%), Central Asian (CAS; 21.1%) and U (17.7%) families were the predominant isolates comprising 69.6% of the total strains. Eighty-five per cent of the U lineage belonged to Spoligo-International-Type (SIT) 910 and SIT 1729. Only a few of these strains are included in SpolDB4 to date. Of the total strains, 41 (17.3%) were unique and have not been described in SpolDB4 to date. This study indicated that the TB epidemic in Amhara Region, Ethiopia, is characterized by the circulation of numerous M. tuberculosis strain families. The high proportion of SIT 910 and SIT 1729 strains may indicate an increase in the importance of these lineages in the transmission of TB in the study region., (© 2013 APMIS. Published by John Wiley & Sons Ltd.)

Background: Data about delayed tuberculosis diagnosis in Northern Russia are scarce yet such knowledge could enhance the care of tuberculosis. The Arkhangelsk region is situated in the north of Russia, where the population is more than one million residents.The aim of the study was to understand factors influencing diagnostic delay among patients with tuberculosis in the Arkhangelsk region and to develop a theoretical model in order to explain diagnostic delay from the patients' perspectives., Methods: Twenty-three patients who had experienced diagnostic delay of tuberculosis were interviewed in Arkhangelsk. Using a qualitative approach, we conducted focus-group discussions for data gathering using Grounded Theory with the Paradigm Model to analyse the phenomenon of diagnostic delay., Results: The study resulted in a theoretical model of the pathway of delay of tuberculosis diagnosis in the Arkhangelsk region in answer to the question: "Why and how do patients in the Arkhangelsk region delay tuberculosis diagnosis?" The model included categories of causal conditions, context and intervening conditions, action/interaction strategies, and consequences. The causal condition and main concern of the patients was that they were overpowered by hopelessness. Patients blamed policy, the administrative system, and doctors for their unfortunate life circumstances. This was accompanied by avoidance of health care, denial of their own health situations, and self-treatment. Only a deadly threat was a sufficient motivator for some patients to seek medical help. "Being overpowered by hopelessness" was identified as the core category that affected their self-esteem and influenced their entire lives, including family, work and social relations, and appeared even stronger in association with alcohol use. This category reflected the passive position of many patients in this situation, including their feelings of inability to change anything in their lives, to obtain employment, or to qualify for disability benefits., Conclusion: The main contributing factor to unsuccessful health-seeking behaviour for patients with tuberculosis was identified as "being overpowered by hopelessness." This should be taken into consideration when creating any preventive programs and diagnostic algorithms aimed at increasing knowledge about TB, improving the health system, decreasing alcohol consumption and reducing the poverty of the people in Arkhangelsk.

Background: Tuberculosis is a major global public health challenge, and a majority of countries have adopted a version of the global strategy to fight Tuberculosis, Directly Observed Treatment, Short Course (DOTS). Drawing on results from research in Ethiopia and Norway, the aim of this paper is to highlight and discuss ethical aspects of the practice of Directly Observed Treatment (DOT) in a cross-cultural perspective., Discussion: Research from Ethiopia and Norway demonstrates that the rigid enforcement of directly observed treatment conflicts with patient autonomy, dignity and integrity. The treatment practices, especially when imposed in its strictest forms, expose those who have Tuberculosis to extra burdens and costs. Socially disadvantaged groups, such as the homeless, those employed as day labourers and those lacking rights as employees, face the highest burdens., Summary: From an ethical standpoint, we argue that a rigid practice of directly observed treatment is difficult to justify, and that responsiveness to social determinants of Tuberculosis should become an integral part of the management of Tuberculosis.

Background: Alcohol has several social consequences that are associated with increased risk of tuberculosis. However, there have been no studies assessing the links between tuberculosis and alcohol consumption in northwest Russia. The aim of this study was to assess associations between the incidence of tuberculosis and indicators of alcohol consumption in three regions of northwest Russia., Methods: The study was performed in Arkhangelsk, Murmansk and Vologda regions using the data from 1975 to 2009. Deaths from alcohol poisoning and the incidence of alcohol psychoses were used as indicators of alcohol consumption. Associations between the incidence of tuberculosis and the above mentioned indicators were studied using time-series analysis., Results: We identified significant positive associations between the incidence of tuberculosis and the incidence of alcohol psychoses in the same year in Arkhangelsk region (β = 0.24, 95% CI: 0.10-0.37) and in Vologda region (β = 0.18, 95% CI: 0.10-0.25), but not in Murmansk region., Conclusions: We found an association between the incidence of alcohol psychoses and the incidence of tuberculosis in the same year in Arkhangelsk and Vologda regions suggesting an indirect link between excessive levels of alcohol consumption and the incidence of tuberculosis in Russia.

Aim: Directly observed treatment (DOT) has been implemented globally as a strategy in treatment of tuberculosis. Studies from high-endemic settings show that DOT involves social and economical burdens for patients, but little is known about experiences with practicing DOT in low-endemic settings. The present study explores patients' and health professionals' views and experiences with DOT in Norway., Method: In-depth interviews were conducted with 22 patients originating from Somalia and Ethiopia and with 20 health professionals. Data from the interviews were analysed using systematic text condensation., Findings: We found that there was little room for patients to negotiate whether or not to consent to the organization of treatment (DOT). Patients told that it was difficult to question the way treatment was organized, as they got the impression that there was no other way of gaining access to medication. Both patients and health professionals reported that persuasion based on authority and subtle threats was used as means to facilitate patients' acceptance of DOT. A majority of patients experienced DOT as humiliating and discriminating, while some had the experience of being cared for. Patients who attended school or had occupational obligations reported high social costs related to the treatment. Patients with positive experiences told that they had been given an opportunity to negotiate flexible treatment schedules and emphasized the importance of continuity among health professionals. Health professionals had divergent views and practices. Some argued that patients should be treated equally, while others argued for an individualized and flexible approach., Conclusion: The practice of DOT reflects societal power structures that influence the clinical interactions between health professionals and patients. To avoid experiences of disempowerment and humiliation among patients, treatment and care should be organized in a way that safeguards patients' right to consent to treatment and that allows patients to negotiate an individualized treatment schedule., (© 2011 The Authors. Scandinavian Journal of Caring Sciences © 2011 Nordic College of Caring Science.)

Drug resistance is a major obstacle to effective TB control program performance. In this study, we assessed the prevalence of primary drug resistance in Mycobacterium tuberculosis (Mtb) isolates in Amhara Region, Ethiopia. A total of 112 Mtb isolates from cases with newly diagnosed pulmonary TB were subjected to drug susceptibility testing (DST) in a cross-sectional study. Isolates were tested for sensitivity to isoniazid, rifampicin, ethambutol, and streptomycin using the MGIT 960 protocol. A total of 93 Mtb isolates yielded valid DST results and 28 (30.1%) were resistant to one or more of first line anti-TB drugs. One isolate (1.0%) was multi-drug resistant (MDR), five (5.4%) were classified as poly-resistant and 22 showed single drug resistance to either streptomycin (n = 19) or isoniazid (n = 3). Isolates from HIV-positive patients were more likely to be resistant to at least one of the four anti-TB drugs compared with HIV-negative individuals (odds ratio 2.76, 95% confidence interval 1.06-7.22; p = 0.03). The study showed a high prevalence of primary drug resistance. Even though the prevalence of MDR was low, conditions that can contribute to the development of MDR are increasing. Therefore, regular monitoring of drug resistance and enhanced implementation of TB/HIV collaborative activities in the study region are imperative., (© 2012 The Authors. APMIS © 2012 APMIS.)

Background: Engaging all health care providers in tuberculosis (TB) control has been incorporated as an essential component of World Health Organization's Stop TB Strategy and the Stop TB Partnership's global plan 2006-2015. Ethiopia has a growing private health sector. The objective of the present study was to investigate the role of private practitioners (PPs) in TB case detection and assess their perspectives on TB treatment delay in Amhara Region, Ethiopia., Results: A cross-sectional study among 112 PPs selected from private health facilities (PHF) in the region was conducted. The study was carried out between May and August 2008 and data was collected using a semi-structured questionnaire. Group differences were analyzed using one-way Anova test and a p-value of < 0.05 was considered statistically significant.In this study, PPs saw a median of 12 TB suspects and 1.5 patients a week. The mean number of TB suspects and patients seen varied significantly among the different professions with p < 0.009 and p < 0.004, respectively. Pulmonary TB patients referred by PPs were delayed up to one week before starting treatment at government health facilities. A 22% increase in the detection of smear-positive TB cases may be achieved by involving all PHFs in the TB control program in the region. Nineteen percent of the PPs indicated that TB patients' prior attendance to non medical health providers resulted in complication of disease and increased treatment delay for TB., Conclusion: PPs manage a substantial number of TB suspects and patients in Amhara Region, Ethiopia. The GHF delay observed among TB patients referred by PPs to GHF is unnecessary. Expanding PPM-DOTS in the region and improving the quality of TB care at both government and private health facilities reduces treatment delay and increases TB case detection.

Background: Knowledge about lay beliefs of etiology, transmission and treatment of TB, and lay perceptions of the relationship between TB and HIV is important for understanding patients' health seeking behavior and adherence to treatment. We conducted a study to explore lay beliefs about TB and TB/HIV co-infection in Addis Ababa, Ethiopia., Findings: We conducted a qualitative study using in-depth interviews with 15 TB/HIV co-infected patients and 9 health professionals and focus group discussions with 14 co-infected patients in Addis-Ababa, Ethiopia. We found that a predominant lay belief was that TB was caused by exposure to cold. Excessive sun exposure, exposure to mud, smoking, alcohol, khat and inadequate food intake were also reported as causes for TB. Such beliefs initially led to self-treatment. The majority of patients were aware of an association between TB and HIV. Some reported that TB could transform into HIV, while others said that the body could be weakened by HIV and become more susceptible to illnesses such as TB. Some patients classified TB as either HIV-related or non-HIV-related, and weight loss was a hallmark for HIV-related TB. The majority of patients believed that people in the community knew that there was an association between TB and HIV, and some feared that this would predispose them to HIV-related stigma., Conclusion: There is a need for culturally sensitive information and educational efforts to address misperceptions about TB and HIV. Health professionals should provide information about causes and treatment of TB and HIV to co-infected patients.

Birds are capable of transporting ticks and, consequently, tick-borne pathogens over long distances and across geographical barriers such as oceans and deserts. The purpose of this study was to assess the prevalence of Borrelia spp. in ticks transported by birds by using PCR. A total of 9768 northward-migrating passerine birds was examined for ticks at 4 bird observatories along the southern Norwegian coast during their spring migration in 2003-2005. Two of the bird observatories were located on islands where flagging revealed very few or no ticks (Akerøya and Store Færder), while the other 2 were located in areas with established dense tick populations: an island, Jomfruland (>100 ticks per hour of flagging) and a mainland locality, Lista (40 ticks in one hour of flagging). Borrelia spp. were found in 70 (13.6%) of 513 examined Ixodes ricinus nymphs (19 B. afzelii, 38 B. garinii, two B. turdi, and 11 B. valaisiana) and in 14 (8.1%) of 172 examined I. ricinus larvae (ten B. garinii, one B. turdi, and three B. valaisiana). This report is the first to identify B. turdi in Europe. Ticks collected from birds of the genus Turdus (T. merula, T. philomelos, and T. iliacus) had a higher prevalence of Borrelia spp. than ticks from the other passerine genera. Ticks that were cofeeding with a Borrelia-infected tick had an increased probability of being infected with the same Borrelia species. Ticks collected on birds from the south-western locality Lista were less likely to have Borrelia than ticks found on birds from the other, more eastern localities. The Turdus spp. are particularly important, both because they carry many ticks per bird and because ticks carried by these species have a higher prevalence of Borrelia. This higher prevalence may be related to Borrelia infection of the birds or transmission of Borrelia through cofeeding. The prevalence of the different Borrelia species in ticks collected from migratory birds may be related to migration routes., (2010 Elsevier GmbH. All rights reserved.)

Background: Tuberculosis is a major public health problem in Ethiopia, and a high number of TB patients are co-infected with HIV. There is a need for more knowledge about factors influencing treatment adherence in co-infected patients on concomitant treatment. The aim of the present study is to explore patients' and health care professionals' views about barriers and facilitators to TB treatment adherence in TB/HIV co-infected patients on concomitant treatment for TB and HIV., Methods: Qualitative study using in-depth interviews with 15 TB/HIV co-infected patients and 9 health professionals and focus group discussions with 14 co-infected patients., Results: We found that interplay of factors is involved in the decision making about medication intake. Factors that influenced adherence to TB treatment positively were beliefs in the curability of TB, beliefs in the severity of TB in the presence of HIV infection and support from families and health professionals. Barriers to treatment adherence were experiencing side effects, pill burden, economic constraints, lack of food, stigma with lack of disclosure, and lack of adequate communication with health professionals., Conclusion: Health professionals and policy makers should be aware of factors influencing TB treatment in TB/HIV co-infected patients on concomitant treatment for TB and HIV. Our results suggest that provision of food and minimal financial support might facilitate adherence. Counseling might also facilitate adherence, in particular for those who start ART in the early phases of TB treatment, and beliefs related to side-effects and pill burden should be addressed. Information to the public may reduce TB and HIV related stigma.

Background: The incidence of bovine babesiosis, caused by Babesia divergens (Apicomplexa: Piroplasmida) has decreased markedly since the 1930 s, but may re-emerge as a consequence of climate change and changes in legislation and pasturing practices. This is a potentially serious disease, with both economical and animal welfare consequences. Therefore, there is a need to survey the distribution of B. divergens., Methods: We tested sera from 306 healthy pastured cows from 24 farms along the southern Norwegian coast by using an indirect immunofluorescence IgG antibody test (IFAT). Fractions of seropositive cows were compared by calculating 95% CI., Results: The results of this test showed that 27% of the sera were positive for B. divergens antibodies. The fraction of antibody-positive sera that we detected showed a two-humped distribution, with a high fraction of positives being found in municipalities in the western and eastern parts of the study area, while the municipalities between these areas had few or no positive serum samples., Conclusions: Neither the farmers' observations nor the Norwegian Dairy Herd Recording System give an adequate picture of the distribution of bovine babesiosis. Serological testing of cows by using IFAT is a convenient way of screening for the presence of B. divergens in an area.

Background: At the dawn of the third millennium, while the control of the second biggest infectious killer in the world (tuberculosis [TB]) is an international priority, millions of pastoralist communities in the Horn of Africa are struggling to access TB care. Prompt diagnosis and treatment of pastoralist TB patients remain to be a challenge in TB control programs in many countries in this region, where pastoralism is a common means of livelihood. Better understanding of community perceptions of TB and its management could help identify reasons for the delay in diagnosis of TB among pastoral communities. The aim of this study is to explore barriers delaying diagnosis among pastoralist TB patients in the Somali Regional State (SRS) of Ethiopia., Methods: A qualitative study, including 19 respondents was conducted in the SRS of Ethiopia. Participatory Rural Appraisal (PRA) and informal interview techniques were employed to explore pastoralists' migration patterns, their perceptions of TB and their access to TB services. The influence of these factors on the delay of TB patients in receiving biomedical diagnosis was then assessed., Results: We found that lack of access to formal health services as well as traditional beliefs leading to self treatment were barriers to prompt bio-medical diagnosis of TB among pastoralist TB patients in the SRS of Ethiopia. This study highlights that limited access to TB control programs is the most important barrier in early seeking of biomedical diagnosis of TB among pastoral communities with nomadic pastoralist being the most affected., Conclusions: Diagnostic and treatment facilities should be established in strategic villages that pastoralist can reach in both dry and wet seasons. Such facilities may alleviate the observed long distance to health facilities and thus long delay in diagnosis of TB. This strategy should be compounded with a community based TB control approach, whereby basic medical training on TB management such as provision of health education, drug distribution and observations is provided to local traditional healers and religious leaders. This approach may improve pastoralists' perceptions of TB, hence eliminating the observed traditional believes associated with TB in pastoralists' context of the SRS.

Background: A major goal of tuberculosis control programs is to stop community transmission of Mycobacterium tuberculosis. However, this can not be rapidly accomplished because, in endemic areas, most of the population is already infected, serving as a reservoir that continuously contributes to the pool of infectious cases. Tuberculin surveys are the main tools used to monitor the infectious pool, but there are serious methodological constraints, and they require resources and expertise that are often unavailable. There is an urgent need for alternative means to monitor the epidemic at the local level., Methodology: We investigated whether a systematic registration of treatment delay in the tuberculosis program records of the Amhara Region of Ethiopia could be utilized to estimate the infectious pool of tuberculosis., Results: The study showed that the total number of infectious days and hence an estimate of the infectious pool could be calculated by recording the treatment delay for new TB cases, retreatment cases and failures, and by estimating the number of undiagnosed cases. Of these categories, treatment delay among new smear-positive tuberculosis cases contributes the greatest number of infectious days., Conclusions: A local tuberculosis program can use a systematic recording of treatment delay as a quantifiable variable to monitor the infectious pool, and can also serve as a key indicator of program performance.

Background: To investigate how the risk of active tuberculosis disease is influenced by time since original infection and to determine whether the risk of reactivation of tuberculosis increases or decreases with age., Methods: Cohort analysis of data for the separate ten year birth cohorts of 1876-1885 to 1959-1968 obtained from Statistics Norway and the National Tuberculosis Registry. These data were used to calculate the rates and the changes in the rates of bacillary (or active) tuberculosis. Data on bacillary tuberculosis for adult (20+) age groups were obtained from the National Tuberculosis Registry and Statistics Norway from 1946 to 1974. Most cases during this period arose due to reactivation of remote infection. Participants in this part of the analysis were all reported active tuberculosis cases in Norway from 1946 to 1974 as recorded in the National Tuberculosis Registry., Results: Tuberculosis decreased at a relatively steady rate when following individual birth cohorts, but with a tendency of slower decline as time passed since infection. A mean estimate of this rate of decline was 57% in a 10 year period., Conclusions: The risk of reactivation of latent tuberculosis decreases with age. This decline may reflect the rate at which latent tuberculosis is eliminated from a population with minimal transmission of tubercle bacilli. A model for risk of developing active tuberculosis as a function of time since infection shows that the rate at which tuberculosis can be eliminated from a society can be quite substantial if new infections are effectively prevented. The findings clearly indicate that preventative measures against transmission of tuberculosis will be the most effective. These results also suggest that the total population harbouring live tubercle bacilli and consequently the future projection for increased incidence of tuberculosis in the world is probably overestimated.

Unlabelled: A pessimistic view of the impact of armed conflicts on the control of infectious diseases has generated great interest in the role of conflicts on the global TB epidemic. Nowhere in the world is such interest more palpable than in the Horn of Africa Region, comprising Ethiopia, Somalia, Eritrea, Djibouti, Kenya and Sudan. An expanding literature has demonstrated that armed conflicts stall disease control programs through distraction of health system, interruption of patients' ability to seek health care, and the diversion of economic resources to military ends rather than health needs. Nonetheless, until very recently, no research has been done to address the impact of armed conflict on TB epidemics in the Somali Regional State (SRS) of Ethiopia., Methods: This study is based on the cross-sectional data collected in 2007, utilizing structured questionnaires filled-out by a sample of 226 TB patients in the SRS of Ethiopia. Data was obtained on the delay patients experienced in receiving a diagnosis of TB, on the biomedical knowledge of TB that patients had, and the level of self-treatment by patients. The outcome variables in this study are the delay in the diagnosis of TB experienced by patients, and extent of self-treatment utilized by patients. Our main explanatory variable was place of residence, which was dichotomized as being in 'conflict zones' and in 'non-conflict zones'. Demographic data was collected for statistical control. Chi-square and Mann-Whitney tests were used on calculations of group differences. Logistic regression analysis was used to determine the association between outcome and predictor variables., Results: Two hundred and twenty six TB patients were interviewed. The median delay in the diagnosis of TB was 120 days and 60 days for patients from conflict zones and from non-conflict zones, respectively. Moreover, 74% of the patients residing in conflict zones undertook self-treatment prior to their diagnosis. The corresponding proportion from non-conflict zones was 45%. Fully adjusted logistic regression analysis shows that patients from conflict zones had significantly greater odds of delay (OR = 3.06; 95% CI: 1.47-6.36) and higher self treatment utilization (OR = 3.34; 95% CI: 1.56-7.12) compared to those from non-conflict zones., Conclusion: Patients from conflict zones have a longer delay in receiving a diagnosis of TB and have higher levels of self treatment utilization. This suggests that access to TB care should be improved by the expansion of user friendly directly observed therapy short-course (DOTS) in the conflict zones of the region.

Setting: Four administrative territories (Archangel Oblast, Murmansk Oblast, Republic of Karelia, Republic of Komi) in the northwestern federal region of Russia., Objective: To describe the genetic diversity and level of drug resistance in Mycobacterium tuberculosis isolates from new cases of pulmonary tuberculosis., Design: A total of 176 isolates of M. tuberculosis were tested for drug susceptibility and typed with insertion sequence (IS) 6110 restriction fragment length polymorphism (RFLP) and spoligotyping., Results: The Beijing family was found to be the most prevalent (47.1%), most frequently clustered and significantly associated with drug resistance to all first-line anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol, streptomycin and pyrazinamide) and ethionamide, when compared to the T and Haarlem families of M. tuberculosis, which were also prevalent in the study population. Some RFLP clusters (4/10) included isolates that originated from patients residing in different territories, and cases infected with multiple strains of M. tuberculosis were apparently present in the collection., Conclusion: The M. tuberculosis population in northwestern Russia appears to be genetically diverse and geographically widespread. Although dominated by isolates assigned to the Beijing family, other families also contribute to the current epidemic, and multiple strain infections may represent a problem in many cases. Extended genetic studies should be encouraged.

Background: We intended to assess the risk for health care workers (HCWs) of acquiring M. tuberculosis infection after exposure to patients with sputum-smear positive pulmonary tuberculosis at three University Hospitals (Ullevål, Akershus, and Haukeland) in Norway., Methods: We tested 155 exposed health care workers and 48 healthy controls both with a tuberculin skin test (Mantoux) and the T-SPOT.TB test, a recently developed interferon-gamma release assays based on the M. tuberculosis-specific ESAT-6 and CFP10 antigens, to investigate if this test might improve infection control measures., Results: Among the 155 exposed HCWs tested in this study, 27 individuals were defined as newly infected cases by TST after recent exposure, while only 3 of these had a positive T-SPOT.TB test. The number of T-SPOT.TB positives represents 11% of the individuals defined as recently infected by TST after exposure (3/27) and 2% of the total number of exposed people tested (3/155). In addition, 15 individuals had been previously defined as infected by TST before exposure of whom 2 subjects were T-SPOT.TB positive. All individuals detected as T-SPOT.TB positive belonged to the TST positive group (> 15 mm), and the percentage concordance between T-SPOT.TB and TST, including both previously and newly infected subjects, was 12% (5/42). The 48 control participants used in the study were all T-SPOT.TB negative, but 3 of these subjects were TST positive., Conclusion: Our data indicate that the frequency of latent TB in the total cohort of HCWs is 3%, whereas the rate of transmission of TB to exposed individuals is approximately 2% and occurs through exposure periods of short duration. Thus, the risk of TB transmission to HCWs following TB exposure in a hospital setting in Norway is low, and improved screening approaches will benefit from the application of specific interferon-gamma release assays.

Management of early tuberculosis (TB) symptoms and adherence to medical treatment are main challenges in controlling TB. The aim of this study is to explore how symptoms of TB are perceived and managed, from the onset of symptoms and during the course of treatment, in Addis Ababa, Ethiopia. We conducted a qualitative interview study, including 50 in-depth interviews and 2 focus groups, with TB patients, their relatives, and health personnel. We found that a patient's perceptions and self-treatment of early symptoms could cause diagnostic delay. Stigma associated with TB and public health services made many patients approach private clinics, causing further delay. Both private and public clinics often labeled and managed symptoms according to lay explanatory models. Lack of adequate knowledge about TB's etiology and cure caused patients to continue relating to symptoms by reference to their own understanding. This affected patients' ability to manage TB and its treatment.

Background: Early diagnosis and immediate initiation of treatment are essential for an effective tuberculosis (TB) control program. Delay in diagnosis is significant to both disease prognosis at the individual level and transmission within the community. Most transmissions occur between the onset of cough and initiation of treatment., Methods: A systematic review of 58 studies addressing delay in diagnosis and treatment of TB was performed. We found different definitions of, for example, debut of symptoms, first appropriate health care provider, time to diagnosis, and start of treatment. Rather than excluding studies that failed to meet strict scientific criteria (like in a meta-analysis), we tried to extract the "solid findings" from all of them to arrive on a more global understanding of diagnostic delay in TB., Results: The main factors associated with diagnostic delay included human immunodeficiency virus; coexistence of chronic cough and/or other lung diseases; negative sputum smear; extrapulmonary TB; rural residence; low access (geographical or sociopsychological barriers); initial visitation of a government low-level healthcare facility, private practitioner, or traditional healer; old age; poverty; female sex; alcoholism and substance abuse; history of immigration; low educational level; low awareness of TB; incomprehensive beliefs; self-treatment; and stigma., Conclusion: The core problem in delay of diagnosis and treatment seemed to be a vicious cycle of repeated visits at the same healthcare level, resulting in nonspecific antibiotic treatment and failure to access specialized TB services. Once generation of a specific diagnosis was in reach, TB treatment was initiated within a reasonable period of time.

Recently, mouse models for latent (LTB) and slowly progressive primary tuberculosis (SPTB) have been established. However, cytokine profiles during the two models are not well established. Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) we studied the expression levels of interleukin (IL)-2, IL-4, IL-10, IL-12, IL-15, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha during the course of LTB and SPTB in the lungs and spleens of B6D2F1Bom mice infected with the H37Rv strain of Mycobacterium tuberculosis (Mtb). The results show that, except for IL-4, cytokine expression levels were significantly higher during SPTB than LTB in both the lungs and spleens. During LTB, all the cytokines (except IL-2 in the lungs) had higher expression levels during the initial period of infection both in the lungs and spleens. During SPTB, the expression levels of IL-15 increased significantly from phases 1 to 3 in the lungs. The expression levels of IL-10, IL-12 and IFN-gamma increased significantly from 2 to 3 in the lungs. IL-10 and IL-15 increased significantly from phases 2 to 3, whereas that of TNF-alpha decreased significantly and progressively from phases 1 to 3 in the spleens. Over-expression of proinflammatory cytokines during active disease has been well documented, but factor(s) underlying such over-expression is not known. In the present study, there was a progressive and significant increase in the expression levels of IL-15, together with Th1 cytokines (IL-12 and IFN-gamma) during SPTB but a significant decrease during LTB. IL-15 is known to up-regulate the production of proinflammatory cytokines, IL-1beta, IL-8, IL-12, IL-17, IFN-gamma and TNF-alpha and has an inhibitory effect on activation-induced cell death. IL-15 is known to be involved in many proinflammatory disease states such as rheumatoid arthritis, sarcoidosis, inflammatory bowel diseases, autoimmune diabetes, etc. Our results, together with the above observations, suggest that IL-15 may play an important role in mediating active disease during Mtb infection.