INT J TUBERC LUNG DIS 18(6):635–639 Q 2014 The Union http://dx.doi.org/10.5588/ijtld.13.0417
The first population-based national tuberculosis prevalence survey in Ethiopia, 2010-2011 A. H. Kebede,* Z. Alebachew,* F. Tsegaye,* E. Lemma,* A. Abebe,* M. Agonafir,* A. J. Kebede,* D. Demissie,* F. Girmachew,* Z. Yaregal,* F. Dana,* M. Getahun,* Y. Fiseha,* A. Meaza,* N. Dirse,* H. Timimi,† C. Sismanidis,† M. Tadolini,‡ I. Onozaki† *Ethiopian Public Health Institute, Addis Ababa, Ethiopia; †Global TB Programme, World Health Organization, Geneva, Switzerland; ‡Infectious Diseases Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy SUMMARY S E T T I N G : Tuberculosis (TB) remains a major public health problem in Ethiopia. O B J E C T I V E : To determine the prevalence of pulmonary TB among the general adult population aged 715 years in 2010–2011. M E T H O D : A nationwide, cluster-sampled, stratified (urban/rural/pastoralist), cross-sectional survey was conducted in 85 selected clusters. All consenting participants were screened for TB using: 1) chest X-ray (CXR) and 2) an interview to screen for symptoms suggestive of TB disease. R E S U LT : Of 51 667 eligible individuals, 46 697 (90%) participated in the survey and completed at least the screening interview. CXR was performed among 46 548 (99.7%) participants. A total of 6080 (13%) partici-
pants were eligible for sputum examination. From the survey, it was estimated that in the national adult population 1) the prevalence of smear-positive TB was 108/100 000 (95%CI 73-143), and 2) that of bacteriologically confirmed TB was 277/100 000 (95%CI 208347). C O N C L U S I O N : We found that the TB burden was lower than previously thought, which may indicate better programme performance. However, a high proportion of TB among young persons suggests that TB is circulating in the community and that there is a need for more efforts to limit the spread of TB disease. K E Y W O R D S : prevalence of TB; bacteriologically confirmed TB; sputum smear positive TB; population-based survey
TUBERCULOSIS (TB) has always been highly prevalent in Ethiopia. According to the 2011 Ministry of Health (MOH) report, TB is the eighth leading cause of hospital admissions and the third leading cause of hospital deaths in Ethiopia.1 In 1992, to prevent and limit the spread of the disease in Ethiopia, the government implemented the DOTS strategy,2 the backbone of global TB control, whose objectives are the diagnosis of 70% of new smearpositive TB cases and achieving 85% cure.3 TB is one of the diseases covered by the sixth Millennium Development Goals (MDGs) with the target of halving TB prevalence and mortality by 2015 compared to 1990 levels.4 TB prevalence is one of the key indicators for the MDGs and the Global Plan to Stop TB. Prevalence surveys have already been conducted in many of the top 22 high TB burden countries.5 Ethiopia has the seventh highest burden of TB globally and ranks third in Africa.6 In a tuberculin
survey conducted in Ethiopia almost six decades ago (1953–1955), the annual risk of infection was 3.0% (unpublished report). The second tuberculin survey, conducted between December 1987 and April 1990, showed a risk of infection of 1.4%, indicating a reduction of 2.2% in comparison to the first study.7,8 Both surveys were limited by the fact that bacteriological parameters had not been used to differentiate tuberculous infection from active disease. According to research conducted on pre-immigration screening of pulmonary TB among Ethiopian migrants to Israel between 1998 and 2005, the point prevalence of pulmonary TB was 170 per 100 000 population.9
MATERIAL AND METHODS A cross-sectional national population-based TB prevalence survey was conducted from October 2010 to June 2011. The following assumptions were made to determine a sample size of 46 514 adults
Correspondence to: Zeleke Alebachew Wagaw, TB Prevalence Survey, Ethiopian Public Health Institute, Arebegnoch St, Addis Ababa 13858, Ethiopia. Tel: (þ251) 911 762 897. Fax: (þ251) 112 780 431. e-mail:
[email protected],
[email protected] Article submitted 26 June 2013. Final version accepted 27 January 2014. [A version in French of this article is available from the Editorial Office in Paris and from the Union website www.theunion.org]
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aged 715 years: the prevalence of smear-positive TB in the adult population was 200/100 000 (30% lower than the World Health Organization [WHO] 2008 estimate [284/100 000] when the survey was designed10); the proportion of adults aged 715 years was 55%; the relative precision with 95% confidence intervals (CI) was 0.2; a design effect of 1.5; a participation rate of 85% and 85 clusters, considering the feasibility of field operations to be conducted in a cluster village within a single week, with a relatively small cluster size of 548 subjects. Of 810 woredas (districts) in Ethiopia, 37 (3% of the total population) were excluded from the study sampling frame due to security and logistical challenges. Multistage cluster sampling using probability proportion to size (PPS) was conducted with three strata (urban, rural and pastoralist) to increase study precision and the accuracy of the results. Numbers of clusters were allocated to each stratum according to the proportion of the population (63 rural, 14 urban and 8 pastoralist). Both districts and kebeles (communes) were selected using PPS. As the population of a kebele is usually larger than the number of required samples per cluster, one part of a kebele was randomly selected from roughly equal-sized parts. During the pre-registration conducted 2 weeks before the cluster activities, all subjects living in the selected households, including adults, children, permanent residents and temporary visitors, were registered. However, only eligible subjects were invited to participate in the survey. The eligibility criteria were age 715 years, permanent residents who had stayed in the household in the last 2 weeks, and temporary visitors who arrived in the household .2 weeks before the census. All eligible study participants who provided informed consent were screened for TB symptoms using one-on-one interviews and underwent antero-posterior CXR for any radiological abnormality in the lung or the mediastinum with a portable unit. A full-size film was developed using an auto-processor immediately after CXR. A trained physician identified abnormal CXRs. Screened persons with symptoms suggestive of TB (cough of 72 weeks) and/or abnormal CXR results were requested to submit two sputum samples (spot and morning) for bacteriological confirmation (Figure 1). Those exempt from CXR but with one of the following criteria were also requested to submit sputum specimens: weight loss .3 kg in the last 1 month, night sweats .2 weeks, fever .2 weeks and contact with a TB patient in the last year. All sputum samples were sent to the National TB Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia. Both spot and morning sputum specimens were examined using light-emitting diode (LED) fluorescence microscopy (Primo Star iLED, Zeiss MicroImaging, Jena, Germany) for acid-fast bacilli (AFB). Culture was performed on all
Figure 1
Tuberculosis screening strategy.
morning specimens; if morning specimens were unavailable, spot samples were used for culture. Lowenstein-Jensen (LJ) medium was used for Myco¨ bacterium tuberculosis culture. Colony morphological characteristics were used to identify M. tuberculosis complex (Capilia TB-Neo Kit, TAUNS Laboratories, Shizuaka, Japan). Quality control of field CXR readings and detailed interpretation of all abnormal field CXR readings were performed at central level. A sample of CXRs consisting of all abnormal images and approximately 10% of normal CXRs were evaluated by independent senior radiologists from St Peter Hospital, Addis Ababa. Prevalent TB cases were identified based on bacteriological results (smear and culture) according to case definitions recommended by the WHO Global Task Force on TB impact measurement.5 After excluding the possibility of cross-contamination, subjects with M. tuberculosis isolated on culture were classified as definite TB cases. Those who were smear-positive without culture confirmation were categorised as probable TB cases if both spot and morning smears were positive or if CXR findings were consistent with TB diagnosed by a consensus panel reading with three or more radiologists or respiratory physicians. Subjects with a single smearpositive result and without abnormal CXR findings were not categorised as prevalent TB cases, although a follow-up examination was prescribed. Those with non-tuberculous mycobacteria (NTM) without an M. tuberculosis co-isolate were also excluded from the prevalent TB case category, regardless of smear and/ or CXR results. Data were entered and cleaned using CSPro statistical package (version 3, US Census Bureau, Washington DC, USA). Analyses were performed using SPSS version 17 (Statistical Product and Service Solutions, Chicago, IL, USA) and Stata version 11 (Stata Corp, College Station, TX, USA). To obtain prevalence estimates, a method with robust standard errors and missing value imputation and inverse probability weighting was applied and adopted as a final result.11
TB prevalence in Ethiopia
Ethical considerations Ethics approval for the study was obtained from the Ethiopian National Ethical Review Committee. All positive participants were linked and referred to the nearest government health facility for treatment and follow-up. Human immunodeficiency virus (HIV) testing was not provided by the study, although detected TB patients were offered HIV testing according to the national guidelines on TB-HIV.2
RESULTS Field data for the first Ethiopian National TB Prevalence Survey were collected from 2 October 2010 to 25 June 2011. A total of 95 092 individuals in
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85 clusters and 19 267 households were selected. Of the selected individuals, 51 667 (54%) were eligible and were invited to participate in the study. Of these, 46 697 (90%) agreed to participate and completed at least the screening interview (Figure 2). The mean age of the participants was 33.6 years. CXR screening was performed in 46 548 (99.7%) participants. Those with symptoms suggestive of TB and/or any abnormality in the lung or mediastinum detected using CXR were eligible for sputum bacteriological examination. Using CXR or symptom screening, 6080 (13%) participants were considered eligible for sputum examination. Of these, 5868 (97%) submitted at least one sputum specimen and 5606 (92%) submitted two specimens (Figure 2).
Figure 2 Survey data flow. * Pregnant, too sick/old, CXR not working. † At least one of fever, weight loss, night sweats or contact with a tuberculosis case. CXR ¼ chest X-ray.
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Sixty-one individuals had at least one positive sputum smear microscopy result using LED fluorescence microscopy. Of these, 13 individuals who did not show any other supportive evidence of TB disease and one with NTM isolates were excluded from the prevalent TB case category. M. tuberculosis was identified in 96 participants, 33 smear-positive and 63 smear-negative. NTM was isolated from 91 participants, 1 of whom was smearpositive and 90 smear-negative, with no M. tuberculosis co-isolate. The survey central panel classified 47 participants as smear-positive TB and 63 as smearnegative, culture-positive TB (i.e., a total of 110 bacteriologically confirmed pulmonary TB cases); 37 (79%) smear-positive and 59 (94%) smear-negative, culture-positive cases were new or previously undetected and had not been previously treated. Only two smear-positive and one smear-negative, culture-positive cases were under treatment at the time of the survey; 12 others had been treated previously but were not undergoing treatment at the time of the survey. More TB patients were observed in younger age groups: of 110 bacteriologically positive TB patients, 60 (58%) were aged ,35 years. The male:female ratio of smear-positive patients was 1.2 (26:21), and that of smear-negative, culture-positive patients was 0.9 (30:33). The prevalence of smear-positive TB among persons aged 715 years was 108/100 000 (95%CI 73-143), whereas the prevalence of bacteriologically confirmed TB in the same age group was 277/100 000 (95%CI 208-347) (Table). TB prevalence among rural, urban and pastoralist populations for both smear-positive pulmonary TB and bacteriologically confirmed TB was comparable. Table Adjusted prevalence (/100 000) of tuberculosis among population aged 715 years, Ethiopia Prevalence of pulmonary TB Smear-positive TB /100 000 (95%CI)
Bacteriologically confirmed TB /100 000 (95%CI)
Stratum Urban Rural Pastoralist
70 (6-135) 109 (67-151) 170 (60-280)
273 (130-416) 273 (189-356) 316 (163-468)
Sex Male Female
133 (80-185) 87 (47-127)
304 (219-388) 246 (176-315)
Age, years 15-24 25-34 35-44 45-54 55-64 765
113 86 117 138 159 41
292 216 259 337 367 227
Overall point prevalence
108 (73-143)
(53-173) (30-143) (43-191) (23-253) (19-300) (11-23)
TB ¼ tuberculosis; CI ¼ confidence interval.
(194-390) (129-303) (135-382) (161-513) (153-582) (33-421)
277 (208-347)
DISCUSSION The First National TB Prevalence Survey in Ethiopia with diagnosis based on CXR screening and culture was successfully conducted along WHO guidelines, with a high population coverage of 97% in sampling, a high participation rate of 90% and a sputum collection rate of 96%. Ethiopia became the first country in Africa to complete the nationwide survey under the guidance of the WHO Global Task Force on TB Impact Measurement. Such a survey had not been conducted in Africa for 50 years. The observed smear-positive TB prevalence of 108 (95%CI 73-143) was much lower than the expected prevalence of 200/100 000 used to calculate the sample size based on WHO estimations when the survey was designed. According to the 2009 WHO Global TB report, the estimated smear-positive pulmonary TB incidence rate in Ethiopia was 163/ 100 000;10 the case detection rate for new smearpositive TB in 2010 was therefore only 36%.12 The results of the first National TB Prevalence Survey show that the magnitude of smear-positive TB is much lower than previous estimates. The main reason for the previous overestimation was likely due to the lack of population-based baseline data; furthermore, HIV prevalence was assumed to be similar to the regional HIV prevalence for sub-Saharan African countries (6%); in reality, this was only 2.3% for Ethiopia during the survey.13 In 2011, 8% of notified TB cases with known HIV status were HIV-positive.14 The expansion of the DOTS strategy may also have contributed to the low observed prevalence of smear-positive TB. Earlier surveys in Asia before DOTS expansion (China 2000, Philippines 1997) have shown that significant proportions of prevalent cases were known cases (i.e., cases under treatment, cases with treatment interruption or chronic).15,16 Our study detected only three patients with bacteriologically positive TB who were currently under treatment and 12 who had been previously treated. The presence of a high-quality nationwide treatment programme was suggested as a reason for this. On the basis of data review, the WHO TB burden estimate for Ethiopia was revised downward. The revised 2011WHO estimate of the case detection rate for the study period was around 72%.17 By generating baseline data, the recently completed TB prevalence survey provides useful information for planning and decision making for the TB control programme in Ethiopia, and will serve as a reference for similar surveys in the future and for pocket studies in specific parts of the country. Although the survey revealed a lower TB prevalence than in previous estimates, the majority of the patients identified by the survey were new cases who had not been captured by the TB control programme. Of concern is the fact that 55% of these previously
TB prevalence in Ethiopia
undetected cases in the community were among the younger age groups (15–34 years), suggesting that interventions are most needed in these sections of the population. The prevalence survey results suggest that TB is circulating in the community, and that the TB epidemic in Ethiopia appears to be occurring in the younger population despite low HIV prevalence among TB patients. There is therefore a need to strengthen community screening for early detection and treatment of cases to reduce TB transmission in the community. More than 50% of the survey cases were smear-negative and identified using culture alone. This highlights the need to widely extend culture diagnostic services. Among all confirmed TB cases, more than 50% did not report chronic cough and were identified using CXR screening. This suggests that CXR is essential for screening active TB in risk groups for earlier detection of a greater number of TB patients. Of 61 subjects with at least one smear-positive result, 14 (23%) were excluded from the prevalent TB patient category. Smear positivity does not always indicate TB disease: in a survey in Eritrea, 12/28 smearpositive cases were excluded after careful follow-up using CXR and three additional smear examinations.18 Careful attention may be required to diagnose TB only by smear examination in prevalence surveys and active case detection in this region. Although quality control was performed, the study had two major limitations: it does not provide information on extra-pulmonary TB cases, which constitute 35% of all notified cases in Ethiopia. Although neck lymph node swellings were assessed during the interview, no bacteriological assessments were performed. Furthermore, children were not included in the study due to technical limitations in screening and diagnosing TB among children. As the survey results and the high proportion of TB in young adults seem to suggest circulation of TB in the community, it is possible that the TB rate in children is higher in Ethiopia than in other countries, where most TB cases are among the elderly. The survey identified several challenges that need to be addressed. The prevalence of culture-positive TB may have been underestimated, as only one specimen per patient was processed for culture. To conclude, the lower TB prevalence observed should not serve as an excuse for reduced efforts or resources allocated for TB control. There is instead a need to further strengthen the programme and effectively tackle TB dissemination in the community until the disease ceases to be a public health threat in Ethiopia. Acknowledgements This study was implemented by the Ethiopian Public Health
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Institute in collaboration with The Federal Ministry of Health of Ethiopia with technical support from the World Health Organization (WHO). In addition, the following organisations have supported the study in various ways: The Global Fund, Geneva, Switzerland; TB Care Ethiopia, United States Agency for International Development Ethiopia, WHO Ethiopia, German Leprosy and TB Relief Association Ethiopia (Addis Ababa, Ethiopia) and Italian Development Cooperation, Rome, Italy. Conflict of interest: none declared.
Reference 1 Federal Democratic Republic of Ethiopia, Ministry of Health. Health and health-related indicators. Addis Ababa, Ethiopia: Federal Ministry of Health, 2011. 2 Federal Democratic Republic of Ethiopia, Ministry of Health. TB, leprosy and TB-HIV control program manual. 4th ed. Addis Ababa, Ethiopia: Federal Ministry of Health, 2008. 3 World Health Organization. Stop TB Strategy: building on and enhancing DOTS to meet the TB-related Millennium Development Goals. WHO/HTM/STB/2006.37. Geneva, Switzerland: WHO, 2006: pp 6–16. 4 United Nations. The Millennium Development Goals Report 2010. New York, NY, USA: UN, 2010. http://www.un.org/ millenniumgoals/aids.shtml Accessed March 2014. 5 World Health Organization. Tuberculosis prevalence surveys: a handbook. WHO/HTM/TB/2011.16. Geneva, Switzerland: WHO, 2011. 6 World Health Organization. Global tuberculosis control: epidemiology, strategy, financing. WHO/HTM/TB/2010.17. Geneva, Switzerland: WHO, 2010. 7 Azbite M. Tuberculin survey in Ethiopia. Kekkaku 1992; 67: 539–544. 8 Azbite M. National Tuberculin Test Survey in Ethiopia. EMJ 1992; 30: 215–224. 9 Mohar Z, Lerman Y, Leventhal A. Pre-immigration screening process and pulmonary tuberculosis among Ethiopian migrants in Israel. Eur Respir J 2008; 32: 413–418. 10 World Health Organization. Global TB database. Geneva, Switzerland: WHO, 2008. 11 Floyd S, Sismanidis C, Yamada N, et al. Analysis of tuberculosis prevalence surveys: new guidance on best-practice methods. Emerg Themes Epidemiol 2013; 10: 10. 12 World Health Organization. Global tuberculosis control: epidemiology, strategy, financing. Annex 3: Country Profile, Ethiopia. WHO/HTM/TB/2009.411. Geneva, Switzerland: WHO, 2009: pp 105–108. 13 Federal Ministry of Health of Ethiopia. TB control programme annual performance report 2010/11. Addis Ababa, Ethiopia: Federal Ministry of Health of Ethiopia, 2011. 14 Ethiopian Health and Nutrition Research Institute. Report on the 2009 Round Antenatal Care Sentinel HIV Surveillance in Ethiopia. Addis Ababa, Ethiopia: Ethiopian Health and Nutrition Research Institute, 2011. 15 Wang L, Zhang H, Ruan Y, et al. Tuberculosis prevalence in China, 1990–2010: a longitudinal analysis of national survey data. Lancet 2014; Mar 14: pii [Epub ahead of print]. 16 Tropical Disease Foundation. Final report Philippines 1997. National Tuberculosis Prevalence Survey. Makati City, The Philippines: Tropical Disease Foundation, 1997. 17 World Health Organization. Global tuberculosis report, 2012. Annex 2: Country Profile, Ethiopia. WHO/HTM/TB/2012.6. Geneva, Switzerland: WHO, 2012: p 113. 18 Mineab S, Bahlbi K, Melles S, et al. Determining the burden of tuberculosis in Eritrea: a new approach. Bull World Health Organ 2007; 85: 593–599.
TB prevalence in Ethiopia
i
RESUME
En Ethiopie la tuberculose (TB) reste un probl`eme de sant´e publique majeur. O B J E C T I F : Determiner la prevalence de TB chez les adultes ag´ ˆ es de 715 ans de la population g´en´erale de 2010 a` 2011. M E T H O D E : Une enqu eˆ te nationale, par grappes, stratifie´ e (urbain/rural/pastoral), transversale a e´ t´e re´ alis e´ e dans 85 grappes s e´ lectionn e´ es. Tous les participants consentants ont b´en´efici´e d’un d´epistage de la TB grace ˆ a` une radio pulmonaire et un entretien a` la recherche de symptomes ˆ compatibles avec la TB. R E´ S U LT A T S : Sur 51 667 individus e´ ligibles, 46 697 (90%) ont particip´e a` l’enquˆete et ont r´epondu au moins au questionnaire. La radio pulmonaire a e´ t´e r´ealis´ee chez CONTEXTE :
46 548 personnes (99,7%). Au total, 6080 participants (13%) e´ taient e´ ligibles pour un examen de crachats. En extrapolant les r´esultats de l’enquˆete, on estime que la pr´evalence de la TB chez les adultes e´ tait de 108/100 000 pour la TB a` frottis positif (IC95% 73–143) et de 277/100 000 pour la TB confirm´ee bact´eriologiquement (IC95% 208–347). C O N C L U S I O N : Nous avons d´ecouvert une charge de morbidit´e li´ee a` la TB inf´erieure a` ce que nous attendions, ce qui pourrait eˆ tre en faveur d’une meilleure performance du programme. Cependant, une proportion e´ lev´ee parmi les jeunes sugg`ere que la TB circule dans la communaut´e et qu’il faut accentuer les efforts pour limiter son expansion. RESUMEN
Etiop´ıa es un pa´ıs donde la tuberculosis (TB) representa todav´ıa un problema de salud publica. ´ O B J E T I V O: Determinar la prevalencia de TB en los ´ general del adultos de 715 anos ˜ de edad de la poblacion 2010 al 2011. M E´ T O D O: Se llevo ´ a cabo una encuesta a escala nacional con muestreo por conglomerados, estratificados (urbano, rural y pastoril) en 85 grupos escogidos. En todos los participantes que lo consintieron se investigo´ la TB mediante la radiograf´ıa de torax ´ y una entrevista en torno a los s´ıntomas indicativos de enfermedad tuberculosa. R E S U LT A D O S: De las 51 667 personas idoneas, ´ 46 697 (90%) participaron en la entrevista y completaron como m´ınimo la entrevista de cribado. Se realizo´ la radiograf´ıa M A R C O D E R E F E R E N C I A:
de torax ´ a 46 548 personas (99,7%). En 6080 de los participantes estaba indicada la baciloscopia (13%). Segun ´ los resultados de la encuesta, se calculo´ que en la poblacion ´ adulta en Etiop´ıa, la prevalencia de TB con baciloscopia positiva fue 108/100 000 habitantes (IC95% 73–143) y la prevalencia de TB confirmada bacteriologicamente ´ fue 277/100 000 (IC95% 208– 347). ´ N: Se observo CONCLUSIO ´ una carga de morbilidad por TB inferior a la prevista, lo cual habla en favor de un mejor desempeno ˜ del programa. No obstante, la alta proporcion ´ de TB en los jovenes ´ indica la presencia de la enfermedad tuberculosa en la colectividad y se requieren medidas tendentes a limitar su transmision. ´
