Many patients remain untreated for tuberculosis

Hamusse S, Demissie M, Teshome D, Hassen MS, Lindtjorn B: Prevalence and Incidence of Smear-Positive Pulmonary Tuberculosis in the Hetosa District of Arsi Zone, Oromia Regional State of Central Ethiopia. BMC Infect Dis 2017, 17:214.

Background  The real burden of smear-positive (PTB+) and bacteriologically confirmed tuberculosis (BCTB) in Ethiopia is not known. Thus, the aim of this community-based study was to measure the prevalence and incidence of tuberculosis in the Hetosa District of Oromia Region, Ethiopia.

Methods  First, a population-based cross-sectional survey was conducted on a total of 33,073 individuals aged ≥ 15 years to determine the prevalence of PTB+ and BCTB cases. Then, in order to determine the incidence, a prospective follow-up was carried out on 32,800 individuals found to be either free from symptoms suggestive of TB (SSTB) during the baseline survey or had symptoms suggestive of TB but yielded negative bacteriological examination results. We identified 1,041 presumptive TB cases at the baseline survey, and 1,468 in the follow-up study. Each participants with cough of more than two weeks were provided spot and morning sputum samples for acid-fast bacilli sputum microscopy and culture.

Results  At the baseline survey, 43 BCTB cases were identified. Thirty six of these were both smear- and culture-positive while seven were only culture-positive. In the follow-up study, however, 76 BCTB cases were diagnosed and 70 of these were found to be both smear- and culture-positive while six were culture-positive only. The adjusted prevalence of PTB+ and BCTB in the study area was 109 and 132/100,000 persons, respectively. Moreover, the incidences of PTB+ and BCTB were 214 and 232/100,000 persons per year (py), respectively. The ratio of the passive to active case finding was 1:0.96 (45/43). For every TB case identified through the existing passive case diagnosis, there was an almost equal number (0.96) of undiagnosed infectious TB cases in the community. A family history of TB contact was independently associated with a high risk of TB (TB prevalence, AOR, 13; 95% CI: 6.55–15.33) and (TB incidence, aIRR 4.11, 95% CI: 2.18–7.77).

Conclusions and recommendations  The prevalence and incidence of smear-positive and bacteriologically confirmed TB cases were high in the study area. For every case of smear-positive TB receiving treatment, there was an almost equal (0.96) number of undetected infectious bacteriologically confirmed TB case in the community. The high proportion of undetected infectious TB cases in the community could possibly be due to the sub-optimal performance of Directly Observed Treatment Short-course (DOTS) in detecting 70% of infectious TB cases, as well as attaining a cure rate of 85% in the study area. Family history of TB contact has substantaially increased the risk of developing the disease, and there is a need to improve ways of identifying TB cases and intensify mechanisms of tracing contacts among household members of PTB+ cases.

Important research on tuberculosis control

Mesay-thesis title

New PhD: On September 5, Mesay Hailu Dangisso from Ethiopia, shall defend his PhD work at the University of Bergen:

Tuberculosis control in Sidama in Ethiopia. Programme performance and spatial epidemiology

The Sustainable Development Goals are to end the TB epidemic by reducing the incidence of TB by 90 % and by reducing mortality by 95% by 2035 from what was in 2015. Globally, access to TB diagnostic and treatment facilities (DOTS) has improved, and millions of TB cases have been notified and treated, which has resulted in many lives being saved. In recent years in Ethiopia, TB control services have been substantially expanded and decentralized, which has improved access to TB care. Assessing trends in TB programme performance (case notification and treatment outcomes), as well as the spatial distribution and variations of the disease, could help in understanding the differentials in accessibility to TB control services, the distribution of disease burden and help in understanding the effectiveness of TB control programmes.

We assessed the distribution of- and accessibility to TB control facilities and trends in TB control programme performance in both urban and rural settings, by age category and by gender, and assessed the case notification rates of childhood TB over 10 years. We also assessed trends of the treatment outcomes of TB cases in order to identify high-risk groups for adverse treatment outcomes. Lastly, we explored spatial distribution and spatio-temporal clustering of the disease over 10 years to identify areas with the highest TB case notifications, and to identify the spatial variations in disease occurrence.

Over 10 years, the accessibility to- and coverage of TB control facilities has improved. Thus, TB control service coverage increased by 36%, and the proportion of locations within 10 km of the nearest TB diagnostic facility also increased. However, we noted variations in physical accessibility between areas in the study area. The mean distance from the nearest smear microscopy unit was 7.6 km in 2003 and declined to 3.2 km in 2012. The substantial expansion of primary health-care services, including TB control facilities and community-based intervention, has contributed to an increase in TB CNRs and treatment outcomes. From this finding, we suggest that a concerted effort be made to improve the accessibility to TB control facilities in areas with low case notification and poor accessibility.

An analysis of the trends of TB case notification and treatment outcomes in different settings based on the correct address, by age category and gender, and place of residence, could help understand the performance of TB control programmes and the epidemiology of TB within a community. We found that the CNRs for all forms of- and smear-positive TB increased steadily between 2003 and 2012. The CNR of smear-positive TB in the 45-year and above age groups rose by nearly fourfold. The disparity between men and women in CNR declined from 16 per 100,000 people in 2003 to eight per 100,000 people in 2012, with the male to female ratio also declining from 1.3:1 to 1.1:1. The increase in CNRs could be attributed to improved access to TB care and community-based interventions.

Over a decade, treatment success increased, whereas mortality and lost-to-follow-up declined. However, more deaths occurred among smear-negative TB cases, in children and among older patients. Targeted interventions are needed to address high-risk groups for adverse treatment outcomes.

The burden of childhood TB is one of the indicators used for assessing the ongoing transmission of the disease within a community. Assessing the case notification and treatment outcome of childhood TB could provide essential evidence to help understand the effectiveness of TB control programmes and the disease burden. Thus, we assessed childhood TB case notification and treatment outcomes over a decade. The mean CNRs for new cases of TB of all forms were 30 per 100,000 children, and no decline was observed in childhood TB cases over a 10-year study period. A community-based active case-finding intervention increased TB case notification in adults and in older children (10-14-year-olds); however, the case notification did not increase among younger children (less than five-years old). This could be explained by inadequate diagnostic facilities for childhood TB despite the community-based intervention, which focuses on symptomatic screening, followed by sputum-smear microscopy and the substantial expansion of TB control services. Better diagnostic facilities and interventions are required to increase case detection, and to improve treatment outcome among younger children.

The burden of TB varies between- and within countries because of differentials in health service performance and the varying distribution of risk factors that increase the transmission of- and susceptibility to the disease. An analysis of the disease burden in coarser geographic or administrative units could hide the burden of the disease at lower administrative units. Therefore, we assessed the distribution of the disease in different geographic settings in the study area, and looked for the pattern of the disease transmission over years, as well as for evidence of spatio- temporal clustering. We found spatial variations in both the disease distribution and spatial and space-time clustering of the disease in the central, northern and northwestern areas of the study area. This could be explained by sustained transmission, disproportionate distribution of risk factors, varying access to TB care and varying TB programme performance, all of which require targeted interventions.

In conclusion, in a population with a high prevalence of tuberculosis, we show that access to tuberculosis diagnostic and treatment facilities, in addition to the performance of TB control programmes, improved from 2003 to 2012. However, we identified areas with poor accessibility to diagnostic and treatment facilities. The low and constant case notification rate in childhood TB is an area of concern, and may indicate an underdiagnosis of childhood tuberculosis. Moreover, the distribution of tuberculosis has changed over time, and in different areas, thereby suggesting a high transmission or variable access to diagnosis and treatment. As a result, the variations in case notification rates, and in accessibility to tuberculosis control services represent challenges on how to improve the organization and performance of TB control.

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Incidence of tuberculosis among school-going adolescents in South India

Uppada DR, Selvam S, Jesuraj N, Lau EL, Doherty TM, Grewal HMS, Vaz M, Lindtjørn B: Incidence of tuberculosis among school-going adolescents in South India. BMC Public Health 2016, 16:1-11.

Background  Tuberculosis (TB) incidence data in vaccine target populations, particularly adolescents, are important for designing and powering vaccine clinical trials. Little is known about the incidence of tuberculosis among adolescents in India. The objective of current study is to estimate the incidence of pulmonary tuberculosis (PTB) disease among adolescents attending school in South India using two different surveillance methods (active and passive) and to compare the incidence between the two groups.

Methods  The study was a prospective cohort study with a 2-year follow-up period. The study was conducted in Palamaner, Chittoor District of Andhra Pradesh, South India from February 2007 to July 2010. A random sampling procedure was used to select a subset of schools to enable approximately 8000 subjects to be available for randomization in the study. A stratified randomization procedure was used to assign the selected schools to either active or passive surveillance. Participants who met the criteria for being exposed to TB were referred to the diagnostic ward for pulmonary tuberculosis confirmation. A total number of 3441 males and 3202 females between the ages 11 and less than 18 years were enrolled into the study.

Results  Of the 3102 participants in the active surveillance group, four subjects were diagnosed with definite tuberculosis, four subjects with probable tuberculosis, and 71 subjects had non-tuberculous Mycobacteria (NTM) isolated from their sputum. Of the 3541 participants in the passive surveillance group, four subjects were diagnosed with definite tuberculosis, two subjects with probable tuberculosis, and 48 subjects had non-tuberculosis Mycobacteria isolated from their sputum. The incidence of definite + probable TB was 147.60 / 100,000 person years in the active surveillance group and 87 / 100,000 person years in the passive surveillance group.

Conclusion  The incidence of pulmonary tuberculosis among adolescents in our study is lower than similar studies conducted in South Africa and Eastern Uganda – countries with a higher incidence of tuberculosis and human immunodeficiency virus (HIV) than India. The study data will inform sample design for vaccine efficacy trials among adolescents in India.

Primary and secondary anti-tuberculosis drug resistance in Ethiopia

Hamusse S, Teshome D, Hussen M, Demissie M, Lindtjorn B. Primary and secondary anti-tuberculosis drug resistance in Hitossa District of Arsi Zone, Oromia Regional State, Central Ethiopia. BMC Public Health 2016; 16(1):

Background: Multidrug-resistant tuberculosis (MDR-TB) drugs which is resistant to the major first-line anti-TB drugs, Isoniazid and Rifampicin, has become a major global challenge in tuberculosis (TB) control programme. However, its burden at community level is not well known. Thus, the aim of study was to assess the prevalence of primary and secondary resistance to any first line anti-TB drugs and MDR TB in Hitossa District of Oromia Regional State, Central Ethiopia.

Methods: Population based cross- sectional study was conducted on individuals aged ≥15 years. Those with symptoms suggestive of TB were interviewed and two sputum specimens were collected from each and examined using Lowenstein-Jensen (LJ) culture medium. Further, the isolates were confirmed by the Ziehl-Neelsen microscopic examination method. Drug susceptibility test (DST) was also conducted on LJ medium using a simplified indirect proportion method. The resistance strains were then determined by percentage of colonies that grew on the critical concentration of Isoniazid, Streptomycin, Rifampicin and Ethambutol.

Results: The overall resistance of all forms of TB to any first-line anti-TB drug was 21.7 %. Of the total new and previously treated culture positive TB cases, 15.3 and 48.8 % respectively were found to be a resistant to any of the first-line anti-TB drugs. Further, of all forms of TB, the overall resistance of MDR-TB was 4.7 %. However, of the total new TB cases, 2.4 % had primary while 14.3 % had secondary MDR-TB. Resistance to any of the first-line anti-TB drugs (adjusted odd ratio (AOR), 8.1; 95 % CI: 2.26–29.30) and MDR-TB (AOR), 7.1; 95 % CI: 2.6–43.8) was found to be linked with previous history of anti-TB treatment.

Conclusions: The study has identified a high rate of primary and secondary resistance to any of the first-line anti-TB drugs and MDR-TB in the study area. The resistance may have resulted from sub-optimal performance of directly observed treatment short-course (DOTS) programme in the detecting infectious TB cases and cure rates in the study area. Anti-TB drug resistance is linked with previous TB treatment. There is a need to strengthen DOTS and DOTS-Plus programmes and expand MDR-TB diagnostic facilities in order to timely diagnose MDR-TB cases and provide appropriate treatment to prevent the spread of MDR-TB in Ethiopia.

Accessibility to TB control services improves in South Ethiopia

Dangisso, M. H., et al. (2015). “Accessibility to tuberculosis control services and tuberculosis programme performance in southern Ethiopia.” Glob Health Action 8: 29443.

BACKGROUND: Despite the expansion of health services and community-based interventions in Ethiopia, limited evidence exists about the distribution of and access to health facilities and their relationship with the performance of tuberculosis (TB) control programmes. We aim to assess the geographical distribution of and physical accessibility to TB control services and their relationship with TB case notification rates (CNRs) and treatment outcome in the Sidama Zone, southern Ethiopia.

DESIGN: We carried out an ecological study to assess physical accessibility to TB control facilities and the association of physical accessibility with TB CNRs and treatment outcome. We collected smear-positive pulmonary TB (PTB) cases treated during 2003-2012 from unit TB registers and TB service data such as availability of basic supplies for TB control and geographic locations of health services. We used ArcGIS 10.2 to measure the distance from each enumeration location to the nearest TB control facilities. A linear regression analysis was employed to assess factors associated with TB CNRs and treatment outcome.

RESULTS: Over a decade the health service coverage (the health facility-to-population ratio) increased by 36% and the accessibility to TB control facilities also improved. Thus, the mean distance from TB control services was 7.6 km in 2003 (ranging from 1.8 to 25.5 km) between kebeles (the smallest administrative units) and had decreased to 3.2 km in 2012 (ranging from 1.5 to 12.4 km). In multivariate linear regression, as distance from TB diagnostic facilities (b-estimate=-0.25, p<0.001) and altitude (b-estimate=-0.31, p<0.001) increased, the CNRs of TB decreased, whereas a higher population density was associated with increased TB CNRs. Similarly, distance to TB control facilities (b-estimate=-0.27, p<0.001) and altitude (b-estimate=-0.30, p<0.001) were inversely associated with treatment success (proportion of treatment completed or cured cases).

CONCLUSIONS: Accessibility to TB control services improved despite the geographic variations. TB CNRs were higher in areas where people had better access to diagnostic and treatment centres. Community-based interventions also played an important role for the increased CNRs in most areas.

Childhood tuberculosis in Ethiopia

Dangisso, MH, Datiko DG and Lindtjørn B. (2015). “Low case notification rates of childhood tuberculosis in southern Ethiopia.” BMC Pediatr 15(1): 1-10.


Background  Childhood tuberculosis (TB) is a public health concern causing considerable mortality. However, control of childhood TB receives little attention. The control efforts could be inadequate because of challenges associated with difficulties in diagnosing the disease in children. Understanding the burden of the disease among children is important to assess the ongoing transmission of the disease in a community and improving TB control efforts. This study was carried out to assess TB case notification rates (CNRs) and treatment outcomes in children aged less than 15 years over a ten-year period.

Methods  Data were collected from unit TB registers from all health facilities providing TB treatment in the Sidama Zone in Ethiopia. We analysed the CNRs and treatment outcomes by age category, gender, and place of residence. We used logistic regression analysis to identify factors associated with treatment outcomes and to control for confounding.

Results  A total of 4,656 cases of children less than 15 years of age were notified as diagnosed and treated for TB, constituting 13 % of all notified TB cases in the study area. The mean CNRs per 100,000 children less than 15 years were 30 for all new cases of TB, 28 for rural cases, 67 for urban cases, 28 in boys, and 32 in girls. The proportions of treatment success were 82 % for new and 77 % for retreatment cases for the entire study period and increased to 93 % for new cases in 2012 (X2 trend, P < 0.001). Children less than five years old had a lower treatment success [adjusted odds ratio (AOR) 0.64 (95 % CI, 0.52-0.80)] and higher deaths [AOR 2 (95 % CI, 1.27–3.12)]. The proportion of children who died during treatment among children in the less than 2-year-old age group was three times higher than children in the 2 year and above age groups [AOR 3.34 (95 % CI, 1.92–5.82)].

Conclusion  The CNRs of childhood TB were low in Sidama. Children less than 5 years old had a higher proportion of deaths. Efforts need to be made to improve the diagnosis and treatment of TB among children.

Spatio-temporal analysis of smear-positive tuberculosis in the sidama zone, southern Ethiopia

Mesay-pone.0126369.g004Dangisso MH, Datiko DG, Lindtjorn B. Spatio-temporal analysis of smear-positive tuberculosis in the sidama zone, southern Ethiopia. PLoS One 2015; 10(6): e0126369.

BACKGROUND: Tuberculosis (TB) is a disease of public health concern, with a varying distribution across settings depending on socio-economic status, HIV burden, availability and performance of the health system. Ethiopia is a country with a high burden of TB, with regional variations in TB case notification rates (CNRs). However, TB program reports are often compiled and reported at higher administrative units that do not show the burden at lower units, so there is limited information about the spatial distribution of the disease. We therefore aim to assess the spatial distribution and presence of the spatio-temporal clustering of the disease in different geographic settings over 10 years in the Sidama Zone in southern Ethiopia.

METHODS: A retrospective space-time and spatial analysis were carried out at the kebele level (the lowest administrative unit within a district) to identify spatial and space-time clusters of smear-positive pulmonary TB (PTB). Scan statistics, Global Moran’s I, and Getis and Ordi (Gi*) statistics were all used to help analyze the spatial distribution and clusters of the disease across settings.

RESULTS: A total of 22,545 smear-positive PTB cases notified over 10 years were used for spatial analysis. In a purely spatial analysis, we identified the most likely cluster of smear-positive PTB in 192 kebeles in eight districts (RR= 2, p<0.001), with 12,155 observed and 8,668 expected cases. The Gi* statistic also identified the clusters in the same areas, and the spatial clusters showed stability in most areas in each year during the study period. The space-time analysis also detected the most likely cluster in 193 kebeles in the same eight districts (RR= 1.92, p<0.001), with 7,584 observed and 4,738 expected cases in 2003-2012.

CONCLUSION: The study found variations in CNRs and significant spatio-temporal clusters of smear-positive PTB in the Sidama Zone. The findings can be used to guide TB control programs to devise effective TB control strategies for the geographic areas characterized by the highest CNRs. Further studies are required to understand the factors associated with clustering based on individual level locations and investigation of cases.

Finding patients with tuberculosis

Woldesemayat EM, Datiko DG, Lindtjørn B. Follow-Up of Chronic Coughers Improves Tuberculosis Case Finding: Results from a Community-Based Cohort Study in Southern Ethiopia. PLoS ONE 2015; 10(2): e0116324.


Untreated smear-positive tuberculosis (TB) patients are the primary source of infection; however, a large number of TB cases have not been identified and are untreated in many sub-Saharan African countries, including Ethiopia. This study determined whether or not a community-based follow-up of chronic coughers improves detection of TB cases and the risk factors for death among such cases.

We conducted a census in six rural communities in Sidama, southern Ethiopia. Based on interview and sputum investigation, we identified 724 TB smear-negative chronic coughers, and did a cohort study of these chronic coughers and 1448 neighbourhood controls. For both chronic coughers and neighbourhood controls, we conducted a TB screening interview and performed sputum microscopy, as required, at 4, 7 and 10 months. Between September 2011 and June 2012, we followed chronic coughers and neighbourhood controls for 588 and 1,204 person-years of observation, respectively.

Of the chronic coughers, 23 developed smear-positive TB (incidence rate = 3912/105 person-years) compared to three neighbourhood controls who developed smear-positive TB (incidence rate = 249/105 person-years). The male-to-female ratio of smear-positive TB was 1:1. We demonstrated that chronic coughers (adjusted hazards ratio [aHR], 13.5; 95% CI, 4.0–45.7) and the poor (aHR, 2.6; 95% CI, 1.1–5.8) were at high-risk for smear-positive TB. Among the study cohort, 15 chronic coughers and two neighbourhood controls died (aHR, 14.0; 95% CI, 3.2–62.4).

A community-based follow-up of chronic coughers is helpful in improving smear-positive TB case detection, it benefits socioeconomically disadvantaged people in particular; in rural settings, chronic coughers had a higher risk of death.

Tuberculosis in South Ethiopia

Mesay-Paper 1Dangisso MH, Datiko DG, Lindtjørn B (2014) Trends of Tuberculosis Case Notification and Treatment Outcomes in the Sidama Zone, Southern Ethiopia: Ten-Year Retrospective Trend Analysis in Urban-Rural Settings. PLoS ONE 9(12): e114225. doi:10.1371/journal.pone.0114225

Background: Ethiopia is one of the high tuberculosis (TB) burden countries. An analysis of trends and differentials in case notifications and treatment outcomes of TB may help improve our understanding of the performance of TB control services. Methods: A retrospective trend analysis of TB cases was conducted in the Sidama Zone in southern Ethiopia. We registered all TB cases diagnosed and treated during 2003–2012 from all health facilities in the Sidama Zone, and analysed trends of TB case notification rates and treatment outcomes.

Results: The smear positive (PTB+) case notification rate (CNR) increased from 55 (95% CI 52.5–58.4) to 111 (95% CI 107.4–114.4) per 105 people. The CNRs of PTB+ in people older than 45 years increased by fourfold, while the mortality of cases during treatment declined from 11% to 3% for smear negative (PTB-) (X2 , trend P,0.001) and from 5% to 2% for PTB+ (X2trend, P,0.001). The treatment success was higher in rural areas (AOR 1.11; CI 95%: 1.03–1.2), less for PTB- (AOR 0.86; CI 95%: 0.80–0.92) and higher for extra-pulmonary TB (AOR 1.10; CI 95%: 1.02– 1.19) compared to PTB+. A higher lost-to-follow up was observed in men (AOR 1.15; CI 95%: 1.06–1.24) and among PTB- cases (AOR 1.14; CI 95%: 1.03–1.25). More deaths occurred in PTB-cases (AOR 1.65; 95% CI: 1.44–1.90) and among cases older than 65 years (AOR 3.86; CI 95%: 2.94–5.10). Lastly, retreatment cases had a higher mortality than new cases (6% vs 3%).

Conclusion: Over the past decade TB CNRs and treatment outcomes improved, whereas the disparities of disease burden by gender and place of residence reduced and mortality declined. Strategies should be devised to address higher risk groups for poor treatment outcomes.