Category Archives: Tuberculosis

Hamusse SD. Tuberculosis Control in Arsi in Ethiopia: Programme Performance and Disease Burden.  PhD. University of Bergen, 2017. Bergen

Tuberculosis (TB) remains a high-priority communicable disease that causes an enormous burden of morbidity and mortality, and infects one-third of the world’s population. It is the second leading cause of death among infectious diseases worldwide, with more than one-fourth of all preventable adult deaths in developing countries due to TB. The disease disproportionately affects people in resource-poor settings, particularly those in Asia and Africa. In addition, more than 80% of TB cases and 78% of deaths occur in developing countries.

The primary causes of the TB epidemic in developing countries are poor socio-economic conditions, an increase in human immuno-deficiency virus and an increase in anti-TB drug resistance, especially the MDR-TB strain. The weak and ineffective national TB control programmes, the poor implementation of infection prevention measures, the poor quality and accessibility to anti-TB drugs, the irrational use of anti-TB treatment regimens and the poor patient adherence are the underlying causes for the emergence of drug- resistant strain including MDR-TB.    The emergence of this strain therefore poses another challenge to TB control efforts.

TB control aims at detecting infectious TB cases as early as possible, and puts them on standardized anti-TB treatment in order to successfully treat and break the chain of transmission and to avert the emergency of multi-drug resistance. The effectiveness of the TB control strategy mainly depends on the timely diagnosis and treatment of smear-positive pulmonary tuberculosis. The cure of smear-positive pulmonary TB patients is considered to be an important intervention mechanism for the primary prevention and emergency of MDR-TB. As a result, a rapid identification of smear-positive pulmonary TB cases and their effective treatment using combined anti-TB drugs is the cornerstone of the global TB control programme.

In 1993, the World Health Organization (WHO) confirmed TB as a global public health emergency and recommended the Directly Observed Treatment, Short Course (DOTS) as a standard strategy to control the disease. In 1994, the World Health Organization designed a Framework for Effective Tuberculosis Control, which clearly designated the core elements of the DOTS strategy. DOTS aims at detecting 70% of infectious TB cases and successfully treating 85% of them to interrupt the transmission, reduce mortality and prevent the emergence of drug resistance.

Ethiopia is among the 22 high-TB-burden countries and the 27 high-MDR-TB-burden worldwide. TB is the leading cause of hospital admission and second leading cause of death in the country. The WHO recommended the DOTS strategy, which was piloted in 1992 and nationally launched in 1995, in a few health facilities with a subsequent expansion to all public health institutions. As a result, in 2015 all public and 14% of private health institutions were covered. The overall aim of this thesis is to assess the trends in TB control performance, and to estimate the burden of the disease at the community level to help achieve a better understanding of the gap in improving the TB control programme in Ethiopia.

The thesis investigates TB control performance, and estimates the disease burden at the community level. The studies focus on assessing trends in TB case notification and treatment outcomes. In addition, we estimate the prevalence, incidence of bacteriologically confirmed TB cases, as well as the burden of primary and secondary drug resistance TB at the community level. The findings of the studies could also be used to explore area-specific strategies help to improve TB control programmes in Ethiopia.

The studies were conducted in Arsi in central Ethiopia, and used cross-sectional and prospective cohort study designs. The studies were conducted in predominantly rural communities and at public health institutions. Most of the papers focus on smear-positive TB, the most infectious form of TB.

The study findings show that the trend in PTB+ case notification increased in parallel with the expansion of DOTS population coverage from 18% to 70% over 15 years. The PTB+ case notification increased from 7 to 63 per 100,000 population in 15 years, with an overall increase of 89%. The TB case detection rate (CDR), estimated by the proportion of PTB+ cases notified from the total annual expected PTB+ incidence of the zone, went up from 6.4% to 58.7% over the study period. The overall 15-year average PTB+ case CDR of the zone was 37.7%, which was far below the 70% global target. Moreover, the PTB+ case notification varied across the 25 districts of the zone. The rural residence and population ratio to DOTS sites and age of the patients were associated with a low TB case notification.

Between 1997 and 2011, the treatment success rates for smear-positive TB rose from 61% to 91%, with a corresponding decline in treatment failure and default rates. The 15-year average cure rate was 67%, which was lower than the global target of an 85% of cure rate. However, treatment outcomes varied across the 25 districts of the zone. The treatment success rate was also found to be associated with the age of the patient, the patient category and TB/HIV co-infection.

Trends in case notification and treatment outcomes are used as proxy indicators to evaluate the TB programme performance. However, to obtain a better understanding of the impact of the TB control programme, we need both baseline and follow-up data on the disease prevalence, incidence and drug resistance burden at the community level. Considering the shortage of resources, we used a less expensive method to estimate the prevalence and incidence of PTB+ and primary and secondary drug resistance, using symptom inquiry followed by sputum microscopy for AFB, culture and a drug-susceptibility test.

The results show that there is a high incidence of PTB+ cases. For every case PTB+ on anti-TB treatment, there was an almost equal number (0.96) of undiagnosed BCTB cases in the community. Furthermore, we identified more men undergoing treatment before the survey, whereas more women were detected during the active TB case finding. The history of TB contact was found to increase the risk of developing active TB, thus suggesting the targeting of contact-tracing among household members diagnosed with PTB+ to help capture the undetected infectious TB cases in the community. The estimation of TB prevalence and incidence based on symptom inquiry and sputum microscopy is a less expensive and simple technique. This method might help to generate information on the magnitude of TB in resource-constrained settings.

We also found that there is a high prevalence of primary and secondary resistance to any one or more first-line anti-TB drugs and primary and secondary MDR-TB in the study area. The highest prevalence of secondary drug resistance was identified among previously treated TB cases compared to primary resistance among new TB cases. This is primarily due to the poor treatment outcomes among previously treated cases caused by lost follow-up and irregularity of drug intake.

The overall 15-year average PTB+ case CDR was 38%, while the cure rate was 67%. So, after 15 years of the DOTS programme, the high proportion of undetected infectious TB cases in the community, combined with increasing primary and secondary drug resistance TB, we conclude that there has been a sub-optimal DOTS performance. Hence, this thesis underscores the need to improve DOTS performance through devising alternative strategies in TB control programmes in Ethiopia.

The thesis can be downloaded here

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.

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.

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.

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

Abstract

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.

Dangisso 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.