1887

Abstract

Studies in Ethiopia have indicated that tuberculosis (TB) patient’s elapsed a long time before initiating treatment.

However, there is very limited evidence on the association of treatment initiation delay with drug resistance.

To investigate the association of delayed treatment initiation with drug resistance among newly diagnosed TB patients in Tigray, Ethiopia.

We conducted a follow-up study from October 2018 to June 2020 by recruiting 875 pulmonary tuberculosis (PTB) patients from 21 randomly selected health facilities. Delays to initiate treatment and drug resistance were collected using a standardized questionnaire and standard laboratory investigation. The association of delay to initiate treatment with acquired drug resistance was modelled using penalized maximum-likelihood (PML) regression models. Data were analysed using software version 15. Statistical significance was reported whenever the -value was less than 0.05.

The median total delay to treatment initiation was 62 days with an inter-quartile range of 16–221 days. A unit change in time to initiate treatment reduced the risk of acquired drug resistance by 3 %. Being smear-positive at the end of treatment and after 2 months of treatment initiation were significantly associated with a higher risk of acquired drug resistance. Whereas, having a mild clinical condition was associated with a lower risk of drug resistance.

Time to treatment initiation delay is associated with an increased risk of the emergence of drug resistance. Efforts targeted towards reducing the negative effects of PTB should focus on reducing the length of delay to initiate treatment.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001814
2024-03-20
2024-04-27
Loading full text...

Full text loading...

References

  1. WHO Global status report on TB 2022. World Health Organization; 2023
  2. Chakaya J, Khan M, Ntoumi F, Aklillu E, Fatima R et al. Global Tuberculosis Report 2020 - Reflections on the Global TB burden, treatment and prevention efforts. Int J Infect Dis 2021; 113 Suppl 1:S7–S12 [View Article]
    [Google Scholar]
  3. Organization WH Global status report on alcohol and health 2018. World Health Organization; 2019
  4. Lee BX, Kjaerulf F, Turner S, Cohen L, Donnelly PD et al. Transforming our World: implementing the 2030 agenda through sustainable development goal indicators. J Public Health Policy 2016; 37 Suppl 1:13–31 [View Article] [PubMed]
    [Google Scholar]
  5. Raviglione M, Director G. Global Strategy and Targets for Tuberculosis Prevention, Care, and Control after 2015 Geneva: World Health Organization; 2013
    [Google Scholar]
  6. FMoH E. Health Sector Transformation Plan Ethiopia: Addis Ababa; 2015
    [Google Scholar]
  7. Menzies D, Pai M, Comstock G. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. Ann Intern Med 2007; 146:340–354 [View Article] [PubMed]
    [Google Scholar]
  8. Sadique MZ, Adams EJ, Edmunds WJ. Estimating the costs of school closure for mitigating an influenza pandemic. BMC Public Health 2008; 8:135 [View Article] [PubMed]
    [Google Scholar]
  9. Odusanya OO, Babafemi JO. Patterns of delays amongst pulmonary tuberculosis patients in Lagos, Nigeria. BMC Public Health 2004; 4:18 [View Article] [PubMed]
    [Google Scholar]
  10. Xu B, Jiang QW, Xiu Y, Diwan VK. Diagnostic delays in access to tuberculosis care in counties with or without the National Tuberculosis Control Programme in rural China. Int J Tuberc Lung Dis 2005; 9:784–790 [PubMed]
    [Google Scholar]
  11. Odusanya OO, Babafemi JO. Patterns of delays amongst pulmonary tuberculosis patients in Lagos, Nigeria. BMC Public Health 2004; 4:1–5 [View Article] [PubMed]
    [Google Scholar]
  12. Mesfin MM, Newell JN, Walley JD, Gessessew A, Madeley RJ. Delayed consultation among pulmonary tuberculosis patients: a cross sectional study of 10 DOTS districts of Ethiopia. BMC Public Health 2009; 9:53 [View Article] [PubMed]
    [Google Scholar]
  13. Mesfin MM, Tasew TW, Tareke IG, Kifle YT, Karen WH et al. Delays and care seeking behavior among tuberculosis patients in Tigray of Northern Ethiopia. Ethiop J Health Dev 2005; 19:I [View Article]
    [Google Scholar]
  14. Hussen A, Biadgilign S, Tessema F, Mohammed S, Deribe K et al. Treatment delay among pulmonary tuberculosis patients in pastoralist communities in Bale Zone, Southeast Ethiopia. BMC Res Notes 2012; 5: [View Article] [PubMed]
    [Google Scholar]
  15. Demissie M, Lindtjorn B, Berhane Y. Patient and health service delay in the diagnosis of pulmonary tuberculosis in Ethiopia. BMC Public Health 2002; 2:23 [View Article] [PubMed]
    [Google Scholar]
  16. Virenfeldt J, Rudolf F, Camara C, Furtado A, Gomes V et al. Treatment delay affects clinical severity of tuberculosis: a longitudinal cohort study. BMJ Open 2014; 4:e004818 [View Article] [PubMed]
    [Google Scholar]
  17. Tedla K, Medhin G, Berhe G, Mulugeta A, Berhe N. Delay in treatment initiation and its association with clinical severity and infectiousness among new adult pulmonary tuberculosis patients in Tigray, northern Ethiopia. BMC Infect Dis 2020; 20:456 [View Article] [PubMed]
    [Google Scholar]
  18. Mor Z, Kolb H, Lidji M, Migliori G, Leventhal A. Tuberculosis diagnostic delay and therapy outcomes of non-national migrants in Tel Aviv, 1998-2008. Euro Surveill 2013; 18:12 [PubMed]
    [Google Scholar]
  19. TRHB Tigray Regional Health Bureau 2017 Annual Report Tigray: Mekelle; 2017
    [Google Scholar]
  20. Ababa A. Federal democratic Republic of Ethiopia. Transport 2016; 1:1
    [Google Scholar]
  21. Berhe G, Enquselassie F, Aseffa A. Treatment outcome of smear-positive pulmonary tuberculosis patients in Tigray Region, Northern Ethiopia. BMC Public Health 2012; 12:537 [View Article] [PubMed]
    [Google Scholar]
  22. Tefera KT, Mesfin N, Reta MM, Sisay MM, Tamirat KS et al. Treatment delay and associated factors among adults with drug resistant tuberculosis at treatment initiating centers in the Amhara regional state, Ethiopia. BMC Infect Dis 2019; 19:489 [View Article] [PubMed]
    [Google Scholar]
  23. Htun YM, Khaing TMM, Yin Y, Myint Z, Aung ST et al. Delay in diagnosis and treatment among adult multidrug resistant tuberculosis patients in Yangon Regional Tuberculosis Center, Myanmar: a cross-sectional study. BMC Health Serv Res 2018; 18:878 [View Article] [PubMed]
    [Google Scholar]
  24. Bagcchi S. WHO’s Global tuberculosis Report 2022. Lancet Microbe 2023; 4:e20 [View Article] [PubMed]
    [Google Scholar]
  25. Tedla K, Medhin G, Berhe G, Mulugeta A, Berhe N. Factors associated with treatment initiation delay among new adult pulmonary tuberculosis patients in Tigray, Northern Ethiopia. PLoS One 2020; 15:e0235411 [View Article] [PubMed]
    [Google Scholar]
  26. Khann S, Mao ET, Rajendra YP, Satyanarayana S, Nagaraja SB et al. Linkage of presumptive multidrug resistant tuberculosis (MDR-TB) patients to diagnostic and treatment services in Cambodia. PLoS One 2013; 8:e59903 [View Article] [PubMed]
    [Google Scholar]
  27. Health FMo Ethiopia-National-Guideline-for-TB-Leprosy-and-DR_TB Addis Ababa; 2018
    [Google Scholar]
  28. Organization WH Global tuberculosis report 2013. World Health Organization; 2013
  29. Organization WH Adherence to long-term therapies: evidence for action. World Health Organization; 2003
  30. Kiros YK, Teklu T, Desalegn F, Tesfay M, Klinkenberg E et al. Adherence to anti-tuberculosis treatment in Tigray, Northern Ethiopia. PHA 2014; 4:S31–6 [View Article] [PubMed]
    [Google Scholar]
  31. Organization WH Guidance for national tuberculosis programs on the management of tuberculosis in children. World Health Organization; 2014
  32. Welekidan LN, Skjerve E, Dejene TA, Gebremichael MW, Brynildsrud O et al. Characteristics of pulmonary multidrug-resistant tuberculosis patients in Tigray Region, Ethiopia: a cross-sectional study. PLoS One 2020; 15:e0236362 [View Article] [PubMed]
    [Google Scholar]
  33. Christianson S, Jamieson F, Sharma MK, Wolfe J. Tuberculosis and mycobacteriology laboratory standards: services and policies. In Canadian Tuberculosis Standards vol 433 2014
    [Google Scholar]
  34. Siddiqi S, Gerdes S. Foundation for Innovative New Diagnostics (FIND) MGITTM Procedure Manual for BACTEC Switzerland: 2006
    [Google Scholar]
  35. Lifescience H. GenoType M. TUBERCULOSISDRplus Ver 2.0 IFU-304A-09 Molecular Genetic Assay for Identification of the M. Tuberculosis Complex and Its Resistance to Rifampicin and Isoniazid from Clinical Specimens and Cultivated Samples Nehren, Germany: Hain Lifescience; 2015
    [Google Scholar]
  36. Zhang Y, Yew W. Mechanisms of drug resistance in Mycobacterium tuberculosis [state of the art series. Drug-resistant tuberculosis. Int J Tuberc Lung Dis 2009; Number 1:1320–1330 in the series
    [Google Scholar]
  37. Leckie G, Charlton C. Runmlwin-a program to run the Mlwin multilevel modeling software from within STATA. J Stat Softw 2013; 52:1–40 [View Article]
    [Google Scholar]
  38. Doerken S, Avalos M, Lagarde E, Schumacher M. Penalized logistic regression with low prevalence exposures beyond high dimensional settings. PLoS One 2019; 14:e0217057 [View Article] [PubMed]
    [Google Scholar]
  39. Rainey C, McCaskey K. Estimating logit models with small samples. In Political Science Research and Methods 2015
    [Google Scholar]
  40. Agonafir M, Lemma E, Wolde-Meskel D, Goshu S, Santhanam A et al. Phenotypic and genotypic analysis of multidrug-resistant tuberculosis in Ethiopia. Int J Tuberc Lung Dis 2010; 14:1259–1265 [PubMed]
    [Google Scholar]
  41. Mekonnen F, Tessema B, Moges F, Gelaw A, Eshetie S et al. Multidrug resistant tuberculosis: prevalence and risk factors in districts of metema and west armachiho, Northwest Ethiopia. BMC Infect Dis 2015; 15:461 [View Article] [PubMed]
    [Google Scholar]
  42. Hamusse SD, Teshome D, Hussen MS, Demissie M, Lindtjørn B. Primary and secondary anti-tuberculosis drug resistance in Hitossa District of Arsi Zone, Oromia Regional State, Central Ethiopia. BMC Public Health 2016; 16:593 [View Article] [PubMed]
    [Google Scholar]
  43. Organization WH Tracking universal health coverage: first global monitoring report: World Health Organization; 2015
  44. Seyoum B, Demissie M, Worku A, Bekele S, Aseffa A. Prevalence and drug resistance patterns of Mycobacterium tuberculosis among new smear positive pulmonary tuberculosis patients in Eastern Ethiopia. Tuberc Res Treat 2014; 2014:753492 [View Article] [PubMed]
    [Google Scholar]
  45. Abate D, Taye B, Abseno M, Biadgilign S. Epidemiology of anti-tuberculosis drug resistance patterns and trends in tuberculosis referral hospital in Addis Ababa, Ethiopia. BMC Res Notes 2012; 5:462 [View Article] [PubMed]
    [Google Scholar]
  46. Tesfay K, Tesfay S, Nigus E, Gebreyesus A, Gebreegziabiher D et al. More than half of presumptive multidrug-resistant cases referred to a tuberculosis referral laboratory in the Tigray region of Ethiopia are multidrug resistant. Int J Mycobacteriol 2016; 5:324–327 [View Article] [PubMed]
    [Google Scholar]
  47. Otu A, Umoh V, Habib A, Ameh S, Lawson L et al. Drug resistance among pulmonary tuberculosis patients in Calabar, Nigeria. Pulm Med 2013; 2013:235190 [View Article] [PubMed]
    [Google Scholar]
  48. Hapolo E, Ilai J, Francis T, du Cros P, Taune M et al. TB treatment delay associated with drug resistance and admission at Daru General Hospital in Papua New Guinea. Public Health Action 2019; 9:S50–S56 [View Article] [PubMed]
    [Google Scholar]
  49. Htun YM, Khaing TMM, Aung NM, Yin Y, Myint Z et al. Delay in treatment initiation and treatment outcomes among adult patients with multidrug-resistant tuberculosis at Yangon Regional Tuberculosis Centre, Myanmar: a retrospective study. PLoS One 2018; 13:e0209932 [View Article] [PubMed]
    [Google Scholar]
  50. Gillespie SH. Evolution of drug resistance in Mycobacterium tuberculosis: clinical and molecular perspective. Antimicrob Agents Chemother 2002; 46:267–274 [View Article] [PubMed]
    [Google Scholar]
  51. Dookie N, Rambaran S, Padayatchi N, Mahomed S, Naidoo K. Evolution of drug resistance in Mycobacterium tuberculosis: a review on the molecular determinants of resistance and implications for personalized care. J Antimicrob Chemother 2018; 73:1138–1151 [View Article] [PubMed]
    [Google Scholar]
  52. Biru D, Woldesemayat EM. Determinants of drug-resistant tuberculosis in Southern ethiopia: a case-control study. Infect Drug Resist 2020; 13:1823–1829 [View Article] [PubMed]
    [Google Scholar]
  53. Djouma FN, Noubom M, Ateudjieu J, Donfack H. Delay in sputum smear conversion and outcomes of smear-positive tuberculosis patients: a retrospective cohort study in Bafoussam, Cameroon. BMC Infect Dis 2015; 15:139 [View Article] [PubMed]
    [Google Scholar]
  54. Gunda DW, Nkandala I, Kavishe GA, Kilonzo SB, Kabangila R et al. Prevalence and risk factors of delayed sputum conversion among patients treated for smear positive PTB in Northwestern rural Tanzania: a retrospective cohort study. J Trop Med 2017; 2017:5352906 [View Article] [PubMed]
    [Google Scholar]
  55. Mesfin EA, Beyene D, Tesfaye A, Admasu A, Addise D et al. Drug-resistance patterns of Mycobacterium tuberculosis strains and associated risk factors among multi drug-resistant tuberculosis suspected patients from Ethiopia. PLoS One 2018; 13:e0197737 [View Article] [PubMed]
    [Google Scholar]
  56. Wang K, Chen S, Wang X, Zhong J, Wang X et al. Factors contributing to the high prevalence of multidrug-resistant tuberculosis among previously treated patients: a case-control study from China. Microb Drug Resist 2014; 20:294–300 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001814
Loading
/content/journal/jmm/10.1099/jmm.0.001814
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error