Effects of Intensive Phase Antituberculous Therapy on Hepatic and Haematological Parameters in Patients at the University Teaching Hospital in Lusaka, Zambia

Glorious Mwaba; Derick Munkombwe; Patrick Kaonga; Mwangana Mubita

doi:10.53974/unza.jabs.4.1.360

Glorious Mwaba Kabwe General Hospital, Department of Pharmacy, P. O. Box, 80917, Kabwe, Zambia.
Derick Munkombwe University of Zambia, School of Health Sciences, Department of Pharmacy, P. O. Box, 50110, Lusaka, Zambia.
Patrick Kaonga 3. University Teaching Hospital, Department of Internal Medicine, P. O. Box, 50110, Lusaka, Zambia.
Mwangana Mubita 4. University of Namibia, Faculty of Health Sciences, School of Pharmacy, Department of Pharmacy Practice and Policy, P/Bag 13301, Windhoek, Namibia

DOI: https://doi.org/10.53974/unza.jabs.4.1.360

Keywords: adverse effects, antituberculous, haematological, hepatic, initial phase, intensive

Abstract

Objectives and study design: Zambia is a high tuberculosis burden country. Antituberculous medicines are the mainstay of tuberculosis management. There have been several reports of antituberculous drug-related haematological and hepatic adverse effects noted in other settings. Adverse events have healthcare cost and morbidity implications. Prevalence and severity of these adverse effects is understudied in patients at University Teaching Hospitals hence the purpose of this study was to identify haematological and hepatic abnormalities and compare parameters before treatment and after completion of intensive phase among the patients. Factors associated with abnormalities were also determined. A prospective longitudinal study was undertaken at Chest Clinic between April 2018 and July 2018. Study patients were followed up for 2 months. Full blood count and liver function tests were recorded at base-line and at follow-up. Abnormalities were defined according to 2017 Department of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events. Data were analysed using SPSS version 22.0 Paired t-test and Wilcoxon matched - pairs signed rank test were used to compare parameters. Logistic regression was performed to determine factors that were predictive of abnormalities. A p< 0.05 was considered statistically significant. Results: A total of 37 patients were involved in the study. 56.8% of patients were male. Mean age of patients was 36.2 years (19 – 57 years) while body mass index was 21.9 kg/m2. Only 37.8% of patients were sputum smear positive at baseline. 56.8% of patients had HIV co-infection. 45.9% of patients were on antiretroviral therapy.45.2% of patients had grade 1-3 aspartate transaminase derangements at follow-up compared to 29.7% at baseline. 5.4% of the patients had grade 1-3 alanine transaminase derangements at baseline while 9.7% of patients had grade 1 at follow-up. Fewer patients (16.1%) had grade 1-2 anaemia at follow-up while 62.2% of patients at baseline had grade 1-4 anaemia. More patients (46.2%) had platelet derangements at follow-up compared to 25.8% at baseline. Fewer patients had differential white cell count derangements at follow-up compared to baseline. Statistically significant differences in haematological parameters: haemoglobin concentration, haematocrit, red, and white cell, eosinophil and neutrophil counts at baseline and follow-up were found. However, no statistical significant differences in red cell indices were observed. Changes in alanine transaminase levels at baseline and follow-up were statistically significant. Logistic regression was performed to determine the effects of age, gender, body mass index, HIV infection, antiretroviral therapy, sputum smear status, and appropriate baseline full blood count/liver function test parameters on the likelihood of study patients having deranged haemoglobin concentration, white cell count and alanine transaminase at follow-up. Logistic regression models to predict deranged haemoglobin concentration and white cell count were statistically insignificant. None of the predictor variables were associated with likelihood of derangements in alanine transaminase. Conclusion: Findings of this study show that haematological and hepatic adverse effects were relatively fewer at follow-up and were mostly grades 1-3 in severity. Antituberculous therapy is relatively safe for patients during the initial phase.

References

1. Glaziou P, Raviglione M, Falzon D, Floyd K. Global epidemiology of tuberculosis. Cold Spring Harb Perspect Med. 2015;5(a017798):7.
2. World Health Organization. Global tuberculosis report 2016. Geneva; 2016.
3. World Health Organization. End TB global tuberculosis report 2017. Geneva; 2017.
4. Morris DWC, Bird RA, Nell H. The haematological and biochemical changes in severe pulmonary tuberculosis. Q J Med. 1990;73(272):1151–9.
5. Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D. Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J RespirCrit Care Med. 2003;167:1472–7.
6. Schaberg T, Rebhan K, Lode H. Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis. EurRespir J. 1996;9(10):2026–30.
7. Lv X, Tang S, Xia Y, Wang X, Yuan Y, Hu D, et al. Adverse reactions due to directly observed treatment strategy therapy in Chinese tuberculosis patients : A prospective study. PLoS One. 2013;8(6):1–8.
8. Long R, Bochar K, Chomyc S, Talbot J, Barrie J, Kunimoto D, et al. Relative versus absolute noncontagiousness of respiratory tuberculosis on treatment. Infect Control HospEpidemiol. 2003;24(11):831–8.
9. Kassa E, Enawgaw B, Gelaw A, Gelaw B. Effect of anti-tuberculosis drugs on hematological profiles of tuberculosis patients attending at University of Gondar Hospital, Northwest Ethiopia. BMC Hematol. 2016;16(1):1–11.
10. An H, Wu X, Wang Z, Xu J, Zheng S, Wang K. The clinical characteristics of anti-tuberculosis drug induced liver injury in 2457 hospitalized patients with tuberculosis in China. African J Pharm Pharmacol. 2013;7(13):710–4.
11. Hassen Ali A, Belachew T, Yami A, Ayen WY. Anti-tuberculosis drug induced hepatotoxicity among TB/HIV co-infected patients at Jimma University Hospital, Ethiopia: Nested case-control study. PLoS One. 2013;8(5):1–8.
12. Abera W, Cheneke W, Abebe G. Incidence of antituberculosis-drug-induced hepatotoxicity and associated risk factors among tuberculosis patients in Dawro Zone, South Ethiopia: A cohort study. Int J Mycobacteriology. 2016;5(1):14–20.
13. Farazi A, Sofian M, Jabbariasl M, Keshavarz S. Adverse reactions to antituberculosis drugs in Iranian tuberculosis patients. Tuberc Res Treat. 2014;2014:1–6.
14. Division of AIDS. Division of AIDS (DAIDS) table for grading the severity of adult and pediatric adverse events. DAIDS AE Grading Table Version 2.1-March 2017. 2017.
15. Bashir BA, Abdallah SA, Mohamedani AA. Anemia among patients with pulmonary tuberculosis in Port Sudan, Eastern Sudan. Int J Recent Sci Res. 2015;6(5):4128–31.
16. Yaranal PJ, Umashankar T, Govindareddy S. Hematological profile in pulmonary tuberculosis. Int J Heal Rehabil Serv. 2013;2(1):50–5.
17. Kapata N, Chanda-Kapata P, Ngosa W, Metitiri M, Klinkenberg E, Kalisvaart N, et al. The prevalence of tuberculosis in Zambia: Results from the first national TB prevalence survey, 2013-2014. PLoS One. 2016;11(1):1–14.
18. Koju D, Rao SB, Shrestha B, Shakya R, Makaju R. Occurrence of side effects from anti - tuberculosis drugs in urban Nepalese population under DOTS treatment. KathanduUnivJounalSci Technol. 2005;1(1):1–4.
19. Enoh JE, Pokam BDT, Eyo AO, Okafor IM, Nguedia CA, Fominyam BT, et al. Drug induced hematological disorders in patients on antituberculosis drugs in the South West Region of Cameroon. Eur J Pharm Med Res. 2017;4(1):155–61.
20. Marra F, Marra CA, Bruchet N, Richardson K, Moadebi S, Elwood RK, et al. Adverse drug reactions associated with first-line anti-tuberculosis drug regimens. Int J Tuberc Lung Dis. 2007;11(8):868–75.
21. Nhamoyebonde S, Leslie A. Biological differences between the sexes and susceptibility to tuberculosis. J Infect Dis. 2014;209(S3):S100-6.
22. Getahun H, Chaisson RE, Raviglione M. Latent mycobacterium tuberculosis infection: Reply. N Engl J Med. 2015;373(12):1179–80.
23. Montales MT, Beebe A, Chaudhury A, Patil N. Mycobacterium tuberculosis infection in a HIV-positive patient. Respir Med Case Reports. 2015;16:160–2.
24. Nagu TJ, Spiegelman D, Hertzmark E, Aboud S, Makani J, Matee MI, et al. Anemia at the initiation of tuberculosis therapy is associated with delayed sputum conversion among pulmonary tuberculosis patients in Dar-es-Salaam, Tanzania. PLoS One. 2014;9(3):1–8.
25. Shang P, Xia Y, Liu F, Wang X, Yuan Y, Hu D, et al. Incidence, clinical features and impact on anti-tuberculosis treatment of anti-tuberculosis drug induced liver injury (ATLI) in China. PLoS One. 2011;6(7):1–7.
26. Gonzalez F, Coughtrie M, Tukey R. Drug Metabolism. In: Brunton L, Hilal-Dandan R, Knollmann B, editors. Goodman & Gilman’s Pharmacological Basis of Therapeutics. 13th ed. New York: McGraw-Hill; 2018. p. 85–100.
27. Pande JN, Singh SP, Khilnani GC, Khilnani S, Tandon RK. Risk factors for hepatotoxicity from antituberculosis drugs: A case-control study. Thorax. 1996;51(2):132–6.
28. Ekhabbazi H, Benkirane R, Khadmaoui A, Sefiani H, Quyou A, Mokhtari A, et al. Evaluation of adverse effects of antituberculosis in El-Idrissi Hospital, Kenitra, Morocco. IOSR J Pharm. 2015;5(1):6–11.