Publications by authors named "Gunnar Bjune"

91 Publications

Exploring the consequences of decentralization: has privatization of health services been the perceived effect of decentralization in Khartoum locality, Sudan?

BMC Health Serv Res 2020 Jul 20;20(1):669. Epub 2020 Jul 20.

Department of Community Medicine, Institute of Health and Society, University of Oslo, Oslo, Norway.

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.
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http://dx.doi.org/10.1186/s12913-020-05511-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370464PMC
July 2020

Mycobacterial antigens accumulation in foamy macrophages in murine pulmonary tuberculosis lesions: Association with necrosis and making of cavities.

Scand J Immunol 2020 Apr 18;91(4):e12866. Epub 2020 Feb 18.

Centre for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.

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.
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http://dx.doi.org/10.1111/sji.12866DOI Listing
April 2020

Traditional healers' role in the detection of active tuberculosis cases in a pastoralist community in Ethiopia: a pilot interventional study.

BMC Public Health 2019 Jun 10;19(1):721. Epub 2019 Jun 10.

Department of Community Medicine and Global Health, Institute for Health and Society, Faculty of Medicine, University of Oslo, P.O. Box 1130, Blindern, 0318, Oslo, Norway.

Background: Pastoralists rely on traditional healers (THs) for general health problems. However, some studies indicate that such practices result in delays in the diagnosis and treatment of tuberculosis (TB) cases. This study aims to assess the role of traditional healers in the detection and referral of active TB cases in a pastoralist community.

Methods: We identified 22 traditional healers from 7 villages of Kereyu pastoralist community in the Fentale district in Ethiopia in January 2015. We trained these THs in identifying presumptive TB symptoms and early referral to the nearby healthcare facilities. The training was held during a 1 week period that included a visit to their villages and follow-up. A 1 day meeting was held with the traditional healers, the district TB care and prevention coordinator and health extension workers from the selected sub-district to discuss the referral link between THs and the nearby healthcare facilities. Health providers working at the TB units in the selected healthcare facilities were oriented about the training given and planned involvement of THs in referring presumptive TB case. In addition, documentation of the presumptive TB cases was discussed.

Results: We succeeded in tracing and interviewing 8 of the 22 THs. The rest were on seasonal migration. According to the THs report for the 1 year period, these 8 THs had referred 24 TB suspects to the healthcare facilities. Sputum smear microscopy confirmed 13 of the 24 suspects as having TB cases. Among those confirmed, 10 completed treatment and three were on treatment. Five presumptive TB cases were confirmed non TB cases through further evaluation at the healthcare facilities and six of the presumptive TB cases were lost to follow up by the THs. Whereas, four of the presumptive TB cases were lost to follow up to the healthcare facility.

Conclusions: Results of the present study indicate that THs can contribute to the detection of undiagnosed active TB cases in a pastoralist community, provided they are given appropriate training and support.
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http://dx.doi.org/10.1186/s12889-019-7074-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558710PMC
June 2019

Integrated Disease Surveillance and Response (IDSR) in Malawi: Implementation gaps and challenges for timely alert.

PLoS One 2018 29;13(11):e0200858. Epub 2018 Nov 29.

Institute of Health and Society, University of Oslo, Oslo City, Norway.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200858PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264833PMC
April 2019

Applying tuberculosis management time to measure the tuberculosis infectious pool at a local level in Ethiopia.

Infect Dis Poverty 2017 Nov 15;6(1):156. Epub 2017 Nov 15.

Amhara Regional State Health Bureau, Bahir Dar, Ethiopia.

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.
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http://dx.doi.org/10.1186/s40249-017-0371-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686949PMC
November 2017

Can a galacto-oligosaccharide reduce the risk of traveller's diarrhoea? A placebo-controlled, randomized, double-blind study.

J Travel Med 2017 Sep;24(5)

Reiseklinikken, St Olavs Plass 3, 0165 Oslo.

Background: Diarrhoea is a common medical problem affecting travellers to Asia, Africa and Latin America. The use of prophylactic antimicrobial agents may increase the risk of contracting resistant bacteria. Findings indicate that oligosaccharides, i.e. carbohydrate chains of 3-10 monosaccharides, reduce the risk of diarrhoea.

Methods: We performed a placebo-controlled, double-blind study of a galacto-oligosaccharide, B-GOS (Bimuno®, Clasado Ltd, Milton Keynes UK), vs placebo for participants travelling to countries with a high/intermediate risk of diarrhoea for 7-15 days. The participants ingested 2.7g of B-GOS daily from 5 days prior to departure throughout the travel period, and returned a questionnaire, with a diarrhoea log, after their return. The case definition of diarrhoea was three or more loose stools per day.

Results: Of 523 enrolled subjects, 334 travellers managed to comply per protocol (PP), 349 followed the protocol at least until the onset of diarrhoea (conditionally evaluable, CE), and 408 followed the protocol with fewer than 5 days of deviance from the protocol (intention to treat, ITT). There was a significant reduction of diarrhoea incidence in the PP group (odds ratio = 0.56, P  =   0.03), while the effect in the CE group was non-significant (OR = 0.65, P  =   0.08). No significant effect was found during the first 7 days after starting with B-GOS, but from day 8 there was a significant effect in both the PP and CE groups (OR = 0.47, P  =   0.02 and OR = 0.53, P  =   0.03, respectively). The entire effect was seen in 1-day (i.e. self-limiting) diarrhoea (PP: OR = 0.25, P  =   0.004). There was no effect on duration or the number of bowel movements during diarrhoea. The severity of diarrhoea was not affected.

Conclusions: B-GOS reduces the risk of diarrhoea lasting 1 day. The protection seemed to start after a week of treatment with B-GOS. Strict compliance is crucial. The treatment is environmentally friendly and without adverse effects.
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http://dx.doi.org/10.1093/jtm/tax057DOI Listing
September 2017

Prevalence and associated factors of tuberculosis and diabetes mellitus comorbidity: A systematic review.

PLoS One 2017 21;12(4):e0175925. Epub 2017 Apr 21.

Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175925PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400500PMC
September 2017

Patients' and health system's delays in the diagnosis and treatment of new pulmonary tuberculosis patients in West Gojjam Zone, Northwest Ethiopia: a cross-sectional study.

BMC Infect Dis 2016 Nov 11;16(1):673. Epub 2016 Nov 11.

Amhara Regional State Health Bureau, Bahir Dar, Ethiopia.

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.
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http://dx.doi.org/10.1186/s12879-016-1995-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106835PMC
November 2016

Total Delay Is Associated with Unfavorable Treatment Outcome among Pulmonary Tuberculosis Patients in West Gojjam Zone, Northwest Ethiopia: A Prospective Cohort Study.

PLoS One 2016 21;11(7):e0159579. Epub 2016 Jul 21.

Amhara Regional State Health Bureau, Bahir Dar, Ethiopia.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159579PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956157PMC
July 2017

Assessment of health system challenges and opportunities for possible integration of diabetes mellitus and tuberculosis services in South-Eastern Amhara Region, Ethiopia: a qualitative study.

BMC Health Serv Res 2016 Apr 19;16:135. Epub 2016 Apr 19.

Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway.

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.
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http://dx.doi.org/10.1186/s12913-016-1378-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837556PMC
April 2016

Qualitative Assessment of Challenges in Tuberculosis Control in West Gojjam Zone, Northwest Ethiopia: Health Workers' and Tuberculosis Control Program Coordinators' Perspectives.

Tuberc Res Treat 2016 15;2016:2036234. Epub 2016 Mar 15.

Institute of Health and Society, University of Oslo, P.O. Box 1130, Blindern, 0318 Oslo, Norway.

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.
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http://dx.doi.org/10.1155/2016/2036234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811263PMC
April 2016

Diabetes mellitus is associated with increased mortality during tuberculosis treatment: a prospective cohort study among tuberculosis patients in South-Eastern Amahra Region, Ethiopia.

Infect Dis Poverty 2016 Mar 21;5:22. Epub 2016 Mar 21.

Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway.

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.
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http://dx.doi.org/10.1186/s40249-016-0115-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806519PMC
March 2016

Prevalence and Associated Factors of Diabetes Mellitus among Tuberculosis Patients in South-Eastern Amhara Region, Ethiopia: A Cross Sectional Study.

PLoS One 2016 25;11(1):e0147621. Epub 2016 Jan 25.

Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147621PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726615PMC
July 2016

Prevalence of tuberculosis, HIV, and TB-HIV co-infection among pulmonary tuberculosis suspects in a predominantly pastoralist area, northeast Ethiopia.

Glob Health Action 2015 18;8:27949. Epub 2015 Dec 18.

Department of Community Medicine, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway.

Background: TB-HIV co-infection is one of the biggest public health challenges in sub-Saharan Africa. Although there is a wealth of information on TB-HIV co-infection among settled populations in Africa and elsewhere, to our knowledge, there are no published reports on TB-HIV co-infection from pastoral communities. In this study, we report the prevalence of TB, HIV and TB-HIV co-infection among pulmonary TB suspects in the Afar Regional State of Ethiopia.

Design: In a cross-sectional study design, 325 pulmonary TB suspects were included from five health facilities. Three sputum samples (spot-morning-spot) were collected from each participant. Sputum samples were examined for the presence of acid fast bacilli using Ziehl-Neelsen staining method, and culture was done on the remaining sputum samples. Participants were interviewed and HIV tested.

Results: Of the 325 pulmonary TB suspects, 44 (13.5%) were smear positive, and 105 (32.3%) were culture positive. Among smear-positive patients, five were culture negative and, therefore, a total of 110 (33.8%) suspects were bacteriologically confirmed pulmonary TB patients. Out of 287 pulmonary TB suspects who were tested for HIV infection, 82 (28.6%) were HIV positive. A significantly higher proportion of bacteriologically confirmed pulmonary TB patients [40 (40.4%)] were HIV co-infected compared with patients without bacteriological evidence for pulmonary TB [42 (22.3%)]. However, among ethnic Afar pastoralists, HIV infections in smear- and/or culture-negative pulmonary TB suspects [7 (7.6%)] and bacteriologically confirmed pulmonary TB patients [4 (11.8%)] were comparable. On multivariable logistic regression analysis, Afar ethnicity was independently associated with low HIV infection [OR=0.16 (95% CI: 0.07-0.37)], whereas literacy was independently associated with higher HIV infection [OR=2.21 (95% CI: 1.05-4.64)].

Conclusions: Although the overall prevalence of TB-HIV co-infection in the current study is high, ethnic Afars had significantly lower HIV infection both in suspects as well as TB patients. The data suggest that the prevalence of HIV infection among Afar pastoralists is probably low. However, population-based prevalence studies are needed to substantiate our findings.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685972PMC
http://dx.doi.org/10.3402/gha.v8.27949DOI Listing
July 2016

IFN-γ and IgA against non-methylated heparin-binding hemagglutinin as markers of protective immunity and latent tuberculosis: Results of a longitudinal study from an endemic setting.

J Infect 2016 Feb 28;72(2):189-200. Epub 2015 Oct 28.

Department of Community Medicine, Institute of Health and Society, University of Oslo, Oslo, Norway.

Background: Heparin-binding hemagglutinin (HBHA) is a surface protein involved in epithelial attachment and extrapulmonary dissemination of Mycobacterium tuberculosis. HBHA is attracting increasing attention for its vaccine and diagnostic potential. In a longitudinal study, we investigated non-methylated, recombinant HBHA-specific cytokine and antibody profiles in cohorts of TB patients, their contacts and community controls in an endemic setting.

Methods: Whole blood assay was done at baseline, 6 and 12 months in patients and contacts, and at entry in controls. ELISA was used to measure IFN-γ, TNF-α and IL-10 (from supernatants), and IgG, IgM and IgA (from sera).

Results: Fifty-three percent of controls and 72.1% of contacts were QFT-GIT positive. Baseline IFN-γ was significantly higher in community controls and contacts compared to untreated TB patients (p < 0.0001). Controls had significantly higher IgA and lower IgM compared to both untreated TB patients and contacts (p < 0.0001). IL-10 was significantly higher in untreated TB patients compared to contacts and controls (p < 0.0001). In treated TB patients, IFN-γ significantly increased (p < 0.0001) whereas IL-10 significantly decreased (p < 0.001).

Conclusion: This study reports for the first time that anti-HBHA IgA could have the potential as a biomarker of protective immunity. In addition, non-methylated, recombinant HBHA-induced IFN-γ could be used as a biomarker of protective immunity and latent TB.
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http://dx.doi.org/10.1016/j.jinf.2015.09.040DOI Listing
February 2016

Lipoarabinomannan-specific TNF-α and IFN-γ as markers of protective immunity against tuberculosis: a cohort study in an endemic setting.

APMIS 2015 Oct 22;123(10):851-7. Epub 2015 Jul 22.

Department of Community Medicine, Institute of Health and Society, University of Oslo, Oslo, Norway.

Lipoarabinomannan (LAM) is a virulent factor used for entry and survival of Mycobacterium tuberculosis (Mtb) in macrophages. Although the role of LAM for the diagnosis of tuberculosis (TB) has been extensively investigated, its cytokine response during natural Mtb infection in humans is largely unknown. In this study, LAM-specific IFN-γ, TNF-α, and IL-10 levels following whole blood assay were measured in untreated pulmonary TB patients, their contacts and community controls at baseline. In treated patients and contacts, cytokines were also measured at 6 and 12 months. At entry, 52.8% and 74.8% of controls and contacts were QFT-GIT positive, respectively. At baseline, untreated TB patients and contacts had significantly lower IFN-γ and TNF-α response compared to community controls (p < 0.0001). Besides, untreated patients had significantly higher TNF-α and IL-10 response compared to their contacts (p < 0.0001). At 6 months, contacts and treated TB patients had significantly increased INF-γ and TNF-α response (p < 0.0001). In TB patients, IFN-γ increased 10-fold following chemotherapy suggesting its potential role for treatment monitoring. The data suggests that LAM might have an anti-inflammatory effect during clinical TB and early Mtb infection. The data also suggests that LAM-induced IFN-γ and TNF-α could be used as biomarkers of protective immunity.
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http://dx.doi.org/10.1111/apm.12423DOI Listing
October 2015

Pro- and anti-inflammatory cytokines against Rv2031 are elevated during latent tuberculosis: a study in cohorts of tuberculosis patients, household contacts and community controls in an endemic setting.

PLoS One 2015 21;10(4):e0124134. Epub 2015 Apr 21.

Department of Community Medicine, Institute of Health and Society, University of Oslo, Oslo, Norway.

Tuberculosis (TB) is among the leading causes of morbidity and mortality. The causative agent, Mycobacterium tuberculosis (Mtb), has evolved virulent factors for entry, survival, multiplication and immune evasion. Rv2031 (also called alpha crystallin, hspX, 16-kDa antigen), one of the most immunogenic latency antigens, is believed to play a key role in long-term viability of Mtb. Here, we report the dynamics of pro-inflammatory (IFN-γ, TNF-α) and anti-inflammatory (IL-10) cytokines against Rv2031 using whole blood assay in human cohorts in a TB endemic setting. Cytokine responses to ESAT-6-CFP-10 were also measured for comparison. Blood samples were collected from smear positive pulmonary TB patients and their contacts at baseline, 6 and 12 months, and from community controls at entry. At baseline, 54.4% of controls and 73.2% of contacts were QFT-GIT test positive. Baseline IFN-γ, TNF-α and IL-10 responses to Rv2031 were significantly higher in controls compared to contacts and untreated patients (p<0.001). Furthermore, untreated patients had significantly higher TNF-α and IL-10 responses to Rv2031 compared to contacts (p<0.001). In contacts and treated patients, IFN-γ, TNF-α and IL-10 responses to Rv2031 significantly increased over 12 months (p<0.0001) and became comparable with the corresponding levels in controls. There was a positive and significant correlation between Rv2031 and ESAT-6-CFP-10 specific cytokine responses in each study group. The fact that the levels of IFN-γ, TNF-α and IL-10 against Rv2031 were highest during latent TB infection may indicate their potential as markers of protection against TB. Taken together, the findings of this study suggest the potential of IFN-γ, TNF-α and IL-10 against Rv2031 as biomarkers of the host response to Mtb during convalescence from, and the absence of, active tuberculosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124134PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405476PMC
April 2016

Mycobacterium tuberculosis lineage 7 strains are associated with prolonged patient delay in seeking treatment for pulmonary tuberculosis in Amhara Region, Ethiopia.

J Clin Microbiol 2015 Apr 11;53(4):1301-9. Epub 2015 Feb 11.

Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Division of Infectious Disease Control, Nydalen, Oslo, Norway.

Recent genotyping studies of Mycobacterium tuberculosis in Ethiopia have reported the identification of a new phylogenetically distinct M. tuberculosis lineage, lineage 7. We therefore investigated the genetic diversity and association of specific M. tuberculosis lineages with sociodemographic and clinical parameters among pulmonary TB patients in the Amhara Region, Ethiopia. DNA was isolated from M. tuberculosis-positive sputum specimens (n=240) and analyzed by PCR and 24-locus mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) analysis and spoligotyping. Bioinformatic analysis assigned the M. tuberculosis genotypes to global lineages, and associations between patient characteristics and genotype were evaluated using logistic regression analysis. The study revealed a high diversity of modern and premodern M. tuberculosis lineages, among which approximately 25% were not previously reported. Among the M. tuberculosis strains (n=138) assigned to seven subgroups, the largest cluster belonged to the lineage Central Asian (CAS) (n=60; 26.0%), the second largest to lineage 7 (n=36; 15.6%), and the third largest to the lineage Haarlem (n=35; 15.2%). Four sublineages were new in the MIRU-VNTRplus database, designated NW-ETH3, NW-ETH1, NW-ETH2, and NW-ETH4, which included 24 (10.4%), 18 (7.8%), 8 (3.5%), and 5 (2.2%) isolates, respectively. Notably, patient delay in seeking treatment was significantly longer among patients infected with lineage 7 strains (Mann-Whitney test, P<0.008) than in patients infected with CAS strains (adjusted odds ratio [AOR], 4.7; 95% confidence interval [CI], 1.6 to 13.5). Lineage 7 strains also grew more slowly than other M. tuberculosis strains. Cases of Haarlem (OR, 2.8; 95% CI, 1.2 to 6.6) and NW-ETH3 (OR, 2.8; 95% CI, 1.0 to 7.3) infection appeared in defined clusters. Intensified active case finding and contact tracing activities in the study region are needed to expedite diagnosis and treatment of TB.
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http://dx.doi.org/10.1128/JCM.03566-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365194PMC
April 2015

High faecal calprotectin levels in intestinal tuberculosis are associated with granulomas in intestinal biopsies.

Infect Dis (Lond) 2015 Mar 18;47(3):137-43. Epub 2014 Dec 18.

Department of Medicine, Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital , Oslo , Norway.

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.
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http://dx.doi.org/10.3109/00365548.2014.974206DOI Listing
March 2015

QuantiFERON-TB Gold In-Tube test conversions and reversions among tuberculosis patients and their household contacts in Addis Ababa: a one year follow-up study.

BMC Infect Dis 2014 Dec 3;14:654. Epub 2014 Dec 3.

Department of Community Medicine, Institute of Health and Society, University of Oslo, P.O. Box 1130, Blindern, 0318, Oslo, Norway.

Background: QuantiFERON-TB Gold In-Tube® (QFT-GIT) test is used for the diagnosis of latent tuberculosis (TB) infection. Besides, QFT-GIT test could allow tracking changes in immune response among TB patients and their contacts. In high TB burden settings, reports on QFT-GIT conversions and reversions among TB patients and their contacts are limited. As part of a major project to study immune responses to TB infection, we investigated QFT-GIT test conversions and reversions among smear positive pulmonary TB patients and their household contacts over 12 months.

Methods: We followed a total of 107 HIV negative participants (33 patients and 74 contacts) in Addis Ababa. We did QFT-GIT test at baseline and 12 months later according to the manufacturer's instructions.

Results: At baseline, 25/33 (75.8%) of the patients and 50/74 (67.6%) of the contacts were QFT-GIT positive. At 12 months, 2 more patients (1 test negative and 1 indeterminate) became test positive. Besides, 11/24 (45.8%) test negative contacts became positive. Only one patient and one contact who were test positive at baseline became test negative 12 months later. At 12 months, the proportions of QFT-GIT test positives for patients and contacts were, therefore, 78.8% and 81.1%, respectively. Among contacts, the proportion of QFT-GIT test positives at 12 months was significantly higher compared to the corresponding proportion at baseline (McNemar, p = 0.006); similarly, the median IFN-γ response significantly increased at 12 months compared with the baseline level (Wilcoxon matched-pairs signed rank test, p = 0.01). Patients, however, had comparable median IFN-γ levels at baseline and 12 months later (p = 0.56).

Conclusion: Nearly half of QFT-GIT negative household contacts at baseline became positive at 12 months. This suggests that repeated screening of QFT-GIT negative contacts may be needed for epidemiological studies and interventions of latent TB in an endemic setting. A large longitudinal study may be needed to confirm our observations.
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http://dx.doi.org/10.1186/s12879-014-0654-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264256PMC
December 2014

Faecal calprotectin levels differentiate intestinal from pulmonary tuberculosis: An observational study from Southern India.

United European Gastroenterol J 2014 Oct;2(5):397-405

Department of Gastroenterology and Hepatology, Institute of Clinical Medicine, Oslo University Hospital Ullevål, Oslo, Norway.

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.
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http://dx.doi.org/10.1177/2050640614546947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212497PMC
October 2014

Two vicious circles contributing to a diagnostic delay for tuberculosis patients in Arkhangelsk.

Emerg Health Threats J 2014 26;7:24909. Epub 2014 Aug 26.

Institute of Health and Society, University of Oslo, Oslo, Norway.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147085PMC
http://dx.doi.org/10.3402/ehtj.v7.24909DOI Listing
March 2015

Routine diagnosis of intestinal tuberculosis and Crohn's disease in Southern India.

World J Gastroenterol 2014 May;20(17):5017-24

Geir Larsson, Department of Medicine, Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, NO-0440 Oslo, Norway.

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.
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http://dx.doi.org/10.3748/wjg.v20.i17.5017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009535PMC
May 2014

A comparison between passive and active case finding in TB control in the Arkhangelsk region.

Int J Circumpolar Health 2014 14;73:23515. Epub 2014 Feb 14.

Institute of Health and Society, University of Oslo, Oslo, Norway.

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.
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http://dx.doi.org/10.3402/ijch.v73.23515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927745PMC
April 2015

Time to first consultation, diagnosis and treatment of TB among patients attending a referral hospital in Northwest, Ethiopia.

BMC Infect Dis 2014 Jan 10;14:19. Epub 2014 Jan 10.

Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Division of Infectious Disease Control, PO Box 4404, Nydalen, 0403 Oslo, Norway.

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.
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http://dx.doi.org/10.1186/1471-2334-14-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898386PMC
January 2014

Tuberculosis management time: an alternative parameter for measuring the tuberculosis infectious pool.

Trop Med Int Health 2014 Mar 7;19(3):313-320. Epub 2014 Jan 7.

Institute of Health and Society, University of Oslo, Oslo, Norway.

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.
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http://dx.doi.org/10.1111/tmi.12246DOI Listing
March 2014

Hopelessness as a basis for tuberculosis diagnostic delay in the Arkhangelsk region: a grounded theory study.

BMC Public Health 2013 Aug 2;13:712. Epub 2013 Aug 2.

Institute for Health and Society, University of Oslo, Oslo, Norway.

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.
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http://dx.doi.org/10.1186/1471-2458-13-712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737145PMC
August 2013

Ethical aspects of directly observed treatment for tuberculosis: a cross-cultural comparison.

BMC Med Ethics 2013 Jul 2;14:25. Epub 2013 Jul 2.

Department of Nursing, Faculty of Health Sciences, Oslo and Akershus University College, PB 4, St. Olavs Plass, 0130, Oslo, Norway.

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.
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http://dx.doi.org/10.1186/1472-6939-14-25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702392PMC
July 2013

Community-based prevalence of undiagnosed mycobacterial diseases in the Afar Region, north-east Ethiopia.

Int J Mycobacteriol 2013 Jun 29;2(2):94-102. Epub 2013 Apr 29.

Department of Community Medicine, Institute for Health and Society, University of Oslo, Norway.

Background: Information on the community-based prevalence of tuberculosis (TB) in different settings is vital for planning, execution and evaluation of strategies to control the disease.

Objective: To assess community-based prevalence of undetected active pulmonary TB (PTB) in pastoralists of the Amibara District.

Methods: Between March and April 2010, a community-based cross-sectional survey of undiagnosed active PTB was conducted in the pastoralists of the Amibara District of the Afar Region, north-east Ethiopia. The study participants were interviewed for symptoms suggestive of PTB using a structured questionnaire. Sputum samples were collected and processed for smear microscopy and culture. Mycobacterium genus typing was performed using a multiplex polymerase chain reaction (PCR).

Results: Out of 222 individuals who had symptoms suggestive of PTB, 4 (1.8%) were found positive by smear microscopy, while mycobacterial growth was observed on 62 (27.9%) samples. Mycobacterium genus typing was carried out for 42 of these 62 samples; 39 (92.9%) gave a positive signal for the genus Mycobacterium. Of these, 23 (59%) isolates proved to be members of the Mycobacterium tuberculosis (Mtb) complex, while the remaining 16 (41.0%) were found to be members of non-tuberculous Mycobacteria (NTM) species.

Conclusion: Sputum culture is highly sensitive, and it is the gold standard for the bacteriological diagnosis of PTB, while smear microscopy is less sensitive to detect acid fast bacilli (AFB) in stained sputum smears. The findings of the present study warrant the strengthening of culture facility services in the study area. The study also provides important preliminary information on the status of NTM infection in the pastoral setting. Nevertheless, further investigations into the species identification of the NTM infections would be useful in the study area.
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http://dx.doi.org/10.1016/j.ijmyco.2013.04.001DOI Listing
June 2013

Why some women fail to give birth at health facilities: a qualitative study of women's perceptions of perinatal care from rural Southern Malawi.

Reprod Health 2013 Feb 8;10. Epub 2013 Feb 8.

Institute of Health and Society, Department of Community Medicine, University of Oslo, Norway, P.O. Box 1130, Blindern, Oslo 0318, Norway.

Background: Despite Malawi government's policy to support women to deliver in health facilities with the assistance of skilled attendants, some women do not access this care.

Objective: The study explores the reasons why women delivered at home without skilled attendance despite receiving antenatal care at a health centre and their perceptions of perinatal care.

Methods: A descriptive study design with qualitative data collection and analysis methods. Data were collected through face-to-face in-depth interviews using a semi- structured interview guide that collected information on women's perception on perinatal care. A total of 12 in- depth interviews were conducted with women that had delivered at home in the period December 2010 to March 2011. The women were asked how they perceived the care they received from health workers before, during, and after delivery. Data were manually analyzed using thematic analysis.

Results: Onset of labor at night, rainy season, rapid labor, socio-cultural factors and health workers' attitudes were related to the women delivering at home. The participants were assisted in the delivery by traditional birth attendants, relatives or neighbors. Two women delivered alone. Most women went to the health facility the same day after delivery.

Conclusions: This study reveals beliefs about labor and delivery that need to be addressed through provision of appropriate perinatal information to raise community awareness. Even though, it is not easy to change cultural beliefs to convince women to use health facilities for deliveries. There is a need for further exploration of barriers that prevent women from accessing health care for better understanding and subsequently identification of optimal solutions with involvement of the communities themselves.
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http://dx.doi.org/10.1186/1742-4755-10-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585850PMC
February 2013