Peposhi I, Tafa H, Bardhi D, Hafizi H. Clinical and epidemiological evaluation of Tuberculosis in Albania during the period 2009-2018 [Original research]. SEEJPH 2020, posted: 16 August 2020. DOI: 10.4119/seejph-3631 P a g e 1 | 10 ORIGINAL RESEARCH Clinical and epidemiological evaluation of Tuberculosis in Albania during the period 2009-2018 Ilir Peposhi1, Holta Tafa1, Donika Bardhi1, Hasan Hafizi1 1University Hospital of Lung Diseases “Shefqet Ndroqi”, Tirana, Albania. Corresponding author: Ilir Peposhi, MD; Address: Rr. “Shefqet Ndroqi”, Tirana, Albania Telephone: +355682090755; Email: ilirpeposhi@yahoo.com Peposhi I, Tafa H, Bardhi D, Hafizi H. Clinical and epidemiological evaluation of Tuberculosis in Albania during the period 2009-2018 [Original research]. SEEJPH 2020, posted: 16 August 2020. DOI: 10.4119/seejph-3631 P a g e 2 | 10 Abstract Aim: To estimate the clinical and epidemiological pattern of Tuberculosis (TB) in Albania over the period 2009-2018. Methods: A retrospective analysis of clinical and epidemiological data based on TB individual notification forms during the period 2009-2018. Results: During the 10-years period, TB incidence increased from 14 to 15.5, but without a sig- nificant increasing trend. The total number of TB cases increased from 440 to 447. The proportion of extra-pulmonary TB decreased from 32% to 25% in 2018 (p=0.015), with and average mean change of 29 cases. Males prevail among TB cases and male-to-female ratio ranges from 2:1 to 3:1. Drug susceptibility testing (DST) was carried out depending on the availability of the reagents and there were 54%, 18% and 96% culture cases confirmed positive in 2009, 2014 and 2019, respectively. The overall treatment completion rate was 85% and 88.2% in 2009 and 2018, respec- tively. However, there was a significant drop in cured cases from 26% in 9.3%, whereas the per- centage of deaths has increased from 0.5% in 4.1%. All treatment outcomes exhibited a significant change (p<0.001). Conclusion: TB continues to be a public health challenge in Albania regardless of the seemingly generally stable epidemiological situation. Keywords: drug resistance, epidemiology, incidence, treatment outcomes, tuberculosis. Conflicts of interest: None declared. Peposhi I, Tafa H, Bardhi D, Hafizi H. Clinical and epidemiological evaluation of Tuberculosis in Albania during the period 2009-2018 [Original research]. SEEJPH 2020, posted: 16 August 2020. DOI: 10.4119/seejph-3631 P a g e 3 | 10 Introduction Tuberculosis (TB) is a communicable disease that is a major cause of ill health, one of the top 10 causes of death worldwide and the leading cause of death from a single infec- tious agent (ranking above HIV/AIDS). TB affects more than 10 million people, causing 1.6 million deaths worldwide and about a quarter of the world’s population is infected with M. Tuberculosis (1). Geographically, most TB cases in 2018 were in the WHO regions of South-East Asia (44%), Africa (24%) and the Western Pacific (18%), with smaller percentages in the East- ern Mediterranean (8%), the Americas (3%) and Europe (3%) (2). Drug-resistant TB continues to be a public health threat. In 2018, there were about half a million new cases of Rifampicin-resistant TB, of which 78% had multidrug-resistant TB (MDR) (3). Despite the notable progress achieved in the fight against TB, countries still face a variety of challenges in reaching the goal to end the epidemic. Proper and fast diagnosis of TB is essential. The sooner a patient is diagnosed, the faster their treatment can begin, easing suffering and preventing further disease transmission. Since 1994, the World Health Organization (WHO) has developed three main strategies for TB prevention and control: directly ob- served treatment short course (DOTS), Stop TB and End TB (4,5). Those strategies fo- cused on case notification and monitoring of treatment outcome as the essential measures to evaluate the effectiveness of interventions and identify potential gaps in TB control (6). The efficacy and successful management of any national tuberculosis control program re- quires reliable clinical and bacteriological di- agnosis. In order to provide these data, a na- tional tuberculosis surveillance system was implemented based on individual data since 2008. Trend in case notification rate, age group af- fected by TB, bacteriological resistance, treatment outcomes and clinical form are the main indicators used to evaluate the National TB Program. All these indicators were ana- lysed in the current study (7-9). The aim of the present study was to estimate the clinical and epidemiological pattern of TB in Albania over the period 2009-2018. Methods The data were obtained from the register at the National Tuberculosis Control Program (NTBP) at the University Hospital of Lung Diseases "Shefqet Ndroqi" (SUSM), Tirana, Albania. Data on tuberculosis patients are recorded and reported individually and in ac- cordance with the guidelines of the World Health Organization and the European TB Supervision Centre (6). The data are collected and reported for each individual patient in accordance with the no- tification reporting form designed in 2001. The notification form includes detailed data on TB and other related factors. The study an- alyse the data reported, recorded and evalu- ated at NTBP and included general patient data, address, sex, occupation, age, diagnosis, direct sputum and culture results, as well as anti-tuberculosis drug sensitivity results and treatment outcomes. Statistical analysis was performed in SPSS 25.0 (Statistical Package for Social Sci- ences). Categorical variables were presented in absolute numbers and corresponding per- centages. Arithmetic averages were calculated for all numerical variables. Differences between groups for discrete variables, nonparametric data, were performed using the Hi-square test. The values of p≤0.05 were considered Peposhi I, Tafa H, Bardhi D, Hafizi H. Clinical and epidemiological evaluation of Tuberculosis in Albania during the period 2009-2018 [Original research]. SEEJPH 2020, posted: 16 August 2020. DOI: 10.4119/seejph-3631 P a g e 4 | 10 significant. Population estimates were based on 2002 census data, with extrapolation. Results Trends analysis of tuberculosis incidence In the study period, the incidence rate of TB per 100,000 inhabitants/year went from 13.4 in 2009 to 14.2 in 2018 (Figure 1); there is no evidence of any significant linear trend in the incidence rate of tuberculosis in Albania in the past decade (P>0.05). The mean percentage of annual changes of TB notification rate from 2009 to 2018 was 6.6%. Figure 1. TB incidence during the period 2009-2018 Tuberculosis cases by site of disease The number of reported cases of pulmonary TB in Albania varies by about 5.3% on aver- age each year, from 2009 to 2018. As a result, the pro- portion of total cases with extra pulmonary decreased from 32% in 2009 to 25% in 2018 (p=0.015, difference between 2009 vs 2018).The average mean change is 29 cases, which shows a stable trend. Figure 2 shows the total number of cases related to site of dis- ease. 14 14 13.5 13.5 16.8 14 14.4 14.4 16.5 15.5 0 2 4 6 8 10 12 14 16 18 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 Peposhi I, Tafa H, Bardhi D, Hafizi H. Clinical and epidemiological evaluation of Tuberculosis in Albania during the period 2009-2018 [Original research]. SEEJPH 2020, posted: 16 August 2020. DOI: 10.4119/seejph-3631 P a g e 5 | 10 Figure 2. Total cases with TB, pulmonary and extra-pulmonary cases Sex and age distribution Males predominate among TB cases in all study period and male: female ratio ranges from 2:1 to 3:1. Young adults (15-44) and the middle-aged (45-64) together represented 76.5% of all cases and respectively 47.4% and 29.1% in 2009. Young adults and the middle-aged rep- resented 73% in 2018, but there was a signif- icant increase in the age group>65 from 19.7% in 2009 to 26.1% in 2018(p=0.014). Table 1. TB by age groups *Chi-square test. 447 445 430 420 474 408 414 413 503 440 305 275 301 312 333 261 296 299 346 330 142 170 129 108 141 147 118 114 157 110 0 100 200 300 400 500 600 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 n o . o f ca se s Total TB cases Pulmonary Ex Pulmonary Age groups Years P-value* 2009 N (%) 2018 N (%) 0-15 18 (4.03) 4 (0.91) 0.002 15-25 86 (19.24) 81 (18.41) 0.409 25-35 63 (14.09) 83 (18.86) 0.034 35-45 62 (13.87) 37 (8.41) 0.006 45-55 71 (15.88) 58 (13.18) 0.148 55-65 59 (13.20) 62 (14.09) 0.386 >65 88 (19.69) 115 (26.14) 0.014 Peposhi I, Tafa H, Bardhi D, Hafizi H. Clinical and epidemiological evaluation of Tuberculosis in Albania during the period 2009-2018 [Original research]. SEEJPH 2020, posted: 16 August 2020. DOI: 10.4119/seejph-3631 P a g e 6 | 10 Figure 3. Distribution (in %) according to age groups There was an increase in the age group 25-34 from 14.2% to 18.8% and in the age group over 65 from 19.4% to 26.1%, while there was a decrease in the age group 35-44 from13.9% to 8.5%. Children accounted re- spectively for 4.1% and 0.9% in 2009 and 2018. Young adults (15-44) and the middle-aged (45-64) together represented 76.5% of all cases and respectively 47.4% and 29.1% in 2009. Young adults and the middle-aged rep- resented 73% in 2018, but there was a signif- icant increase in age group >65 in 2018(p=0.014). Bacteriological confirmation and drug sus- ceptibility testing The proportion of bacteriologically con- firmed cases remained high during the study period and there was not great variation an- nually in smear confirmation cases. Average mean change was 17 ± 13 cases per year, which shows a constant trend. Drug susceptibility testing (DST) was carried out in a small proportion of pulmonary TB cases, only for 30% of cases in 2018 due to shortage of reagent. The number of cultures tested dropped from 201 in 2009 to 63 in 2018, but starting from 2013 the number of tests was reduced dramatically, and conse- quently the MDR data are not reliable for our country. 4.1 19.3 14.2 13.9 15.8 13.3 19.4 0.9 18.4 18.8 8.5 13.2 14.1 26.1 0-14 15-24 25-34 35-44 45-54 55-64 >65 Year 2009 Year 2018 Peposhi I, Tafa H, Bardhi D, Hafizi H. Clinical and epidemiological evaluation of Tuberculosis in Albania during the period 2009-2018 [Original research]. SEEJPH 2020, posted: 16 August 2020. DOI: 10.4119/seejph-3631 P a g e 7 | 10 Table 2. Proportion of smear positive cases, MDR and number of drug susceptibility testing Year PTB Smear positive % of smear positive MDR cases DST 2009 305 192 63% 0 201 2010 275 165 60% 2 182 2011 301 190 63% 5 203 2012 312 206 66% 0 163 2013 333 212 64% 1 27 2014 261 175 67% 2 29 2015 296 209 71% 3 13 2016 299 206 69% 1 40 2017 346 210 61% 0 79 2018 330 208 63% 2 63 Treatment outcomes The overall treatment success rate was 85% and 88.2% in 2009 and 2018, respectively. There is a significant drop in cured cases in 2009 from 26% to 9.3% in 2018. Also, the percentage of deaths increased from 0.5% to 4.1%. All treatment outcomes displayed a significant change (p<0.001). Figure 4. Treatment outcomes (in percent) 25.95 59.60 0.50 2.90 11.40 9.31 78.86 4.10 0.23 7.50 Cured Treatment completed Dead Failure Lost to follow up 2018 2009 Peposhi I, Tafa H, Bardhi D, Hafizi H. Clinical and epidemiological evaluation of Tuberculosis in Albania during the period 2009-2018 [Original research]. SEEJPH 2020, posted: 16 August 2020. DOI: 10.4119/seejph-3631 P a g e 8 | 10 Discussion The number of patients diagnosed with tuber- culosis in the study period had a slight oscil- lation with an insignificant trend of increase in TB incidence. The incidence increased from 13.4% in 2008 to 15.3% in 2018. There was no evidence of a trend and a statistically significant change in the incidence rate over the study period. The incidence of TB ap- pears to be more or less stable, but if we com- pare it with the neighbouring countries or other European countries, we notice that Al- bania is the only country in the region with increased TB incidence and a positive mean annual change (Table 3). There is a wide var- iation in TB incidence in the Balkan region from 4 (Greece) to 39 (Kosova) cases per 100,000 population. Table 3. TB incidence in the Balkan region Country TB incidence 2009 (cases per 100,000) TB incidence 2018 MACH* 2014-2018 Albania 13.4 15.3 2.0% Kosova 60 39.2 -4.6% Montenegro 19.2 13.4 -7.2% North Macedonia 23.2 10.4 -6.6% Serbia 17.2 9.4 -7.0% Grecee 5.2 4 -4.1% This indicates that stability of TB incidence over the years in Albania is not a good TB programme indicator and the National TB Programme has to analyse the cause of this stagnation. Furthermore, despite the stable incidence, the proportion of pulmonary TB cases increased to 75% in 2018, posing a se- rious risk of spreading cases with infectious TB and consequently increasing TB inci- dence in coming years. The proportion of extra pulmonary TB con- tinues to be high despite the significant de- crease during the last years. The lowest pro- portion 25% was in 2018 and the higher was 38% in 2010. There is a stable trend in de- creasing the proportion of extra pulmonary cases, although the proportion remains high compared to the region. The proportion of ex- tra-pulmonary TB was 14% in Greece, 11% in Serbia, 12% in Monte Negro, 24% in North Macedonia and 29% in Kosovo in 2019. The variances in the reporting of extra-pulmonary TB may result from different diagnostic prac- tices across the country in the region or epi- demiological factors and the prevailing M. TB strains (10). Males predominate among TB cases in all study period and male: female ratio ranges from 2:1 to 3:1. There were twice as many males as females reported among all incident TB cases in Eu- ropean region, but large variation was ob- served for male predominance in the sex dis- tribution of TB cases, ranging from almost an even distribution to over three times greater in Armenia and Albania. There are few pub- lications on TB gender differences world- wide and it is not clear whether the differ- ences in morbidity between the sexes are due to biological factors, socioeconomic context, or under diagnosis of TB in women who are Peposhi I, Tafa H, Bardhi D, Hafizi H. Clinical and epidemiological evaluation of Tuberculosis in Albania during the period 2009-2018 [Original research]. SEEJPH 2020, posted: 16 August 2020. DOI: 10.4119/seejph-3631 P a g e 9 | 10 likely to have the least access to health care (11,12). In Albania, the disease of tuberculo- sis continues to be an important cause of mor- bidity in women. The differences between the sexes have been constantly ascertained, but there is no study to assess these changes (13). Bacteriological confirmation of TB diagnosis was high during the study period, over 60%, and there was not great variation annually in smear confirmation cases. A high proportion of bacteriologically con- firmed PTB cases might imply a delay in di- agnosis and may reflect several gaps in diag- nosis, such as lack of capacity by the program to accurately diagnose TB through bacterio- logical examination (14). The proportion of bacteriologically con- firmed cases among pulmonary TB varied considerably among the countries in the re- gion from 45% in Kosovo to 95% in Serbia. The increasing proportion in other countries in the region is due to the implementation of the new technology in these countries, specif- ically GeneXpert. Thus, the proportion of bacteriologically confirmed cases before and after application of GeneXpert in Monte Ne- gro was 59% and 86% respectively, in Bosnia and Herzegovina 42% and 74% and in North Macedonia 65% and 90%, respectively. Al- bania has installed last year two GeneXpert and we expect an increase in the bacteriolog- ical confirmation like in other neighbouring countries (15). MDR-TB is a major issue in the Balkan re- gion with the percentage of MDR-TB among all TB cases increasing over the last 10 years from 4.3% to 7.5% (16). Drug susceptibility testing was carried out in a small proportion of pulmonary TB cases (only for 30% of the cases) and we cannot analyse this important indicator, but the proportion of MDR re- sistance remains low (less than 3% over the study period). Albanian government must provide the necessary reagent for performing drug susceptibility test and evaluating the real situation of MDR in Albania. Over the study period, the treatment success rates continued to improve, but the cure rate decreased significantly due to the lack of bac- teriological confirmation during the follow up treatment phase. The number of deaths in- creased, but there are only few numbers to draw a valid statistical conclusion. Conclusion Despite the stagnation of the total number of TB cases during the study period, the epide- miological situation should not be assessed as stable, but deteriorating. MDR situation is unknown due to the shortage of reagent and pose a threat to TB control. The other epide- miological indicators like treatment out- comes and age group improved during the study period. References 1. World Health Organization (WHO). Global tuberculosis report 2018. Ge- neva: WHO; 2018. Available from: https://apps.who.int/iris/bitstream/han- dle/10665/274453/9789241565646- eng.pdf?sequence=1&isAllowed=y (ac- cessed: August 1, 2019). 2. World Health Organization. Moscow Declaration to End TB; First WHO global ministerial conference on ending TB in the sustainable development era: a multisectoral response. Geneva: World Health Organization and the Ministry of Health of the Russian Federation; 2017. 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