Relationship between C-reactive protein, ferritin serum and cluster of differentiation 4 cell count with pulmonary tuberculosis in naive HIV patient in Bali


  • Ida Bagus Putu Adi Styawan Department Pulmonology and Respiratory Medicine, Udayana University, Denpasar, Bali, Indonesia
  • I Ketut Agus Somia Department of Internal Medicine, Udayana University, Denpasar, Bali, Indonesia
  • Ni Wayan Candrawati Department Pulmonology and Respiratory Medicine, Udayana University, Denpasar, Bali, Indonesia
  • Ida Ayu Jasminarti Dwi Kusumawardani Department Pulmonology and Respiratory Medicine, Udayana University, Denpasar, Bali, Indonesia
  • Ni Luh Putu Eka Arisanti Department Pulmonology and Respiratory Medicine, Udayana University, Denpasar, Bali, Indonesia
  • I Gusti Ngurah Bagus Artana Department Pulmonology and Respiratory Medicine, Udayana University, Denpasar, Bali, Indonesia
  • Ida Bagus Ngurah Rai Department Pulmonology and Respiratory Medicine, Udayana University, Denpasar, Bali, Indonesia



C-reactive protein, Ferritin serum, CD4 cell count, Pulmonary tuberculosis, Naive HIV infection


Background: Diagnostic of Pulmonary tuberculosis (PTB) in patients with Human immunodeficiency virus (HIV) infection remain challenging. Evaluation based on clinical symptoms, inflammation biomarkers, and immunodeficiency status, can provide a feature of PTB disease in HIV patient. The aim of the study was to analyze the relationship between acute phase reactant and immunodeficiency status with PTB in patients with naïve HIV infection.

Methods: A cross sectional study was conducted in Sanglah General Hospital and Kuta Selatan Public Health Service on February-June 2021. C-reactive protein (CRP), Ferritin serum levels, and CD-4 cell count were obtained from patient's serum. Data were collected by questionnaire. Bivariate analysis using Chi square test or Kolmogorov Smirnov test, and multivariate analysis using logistic regression.

Results: A total of 60 participants were included in this study, and 58.3% had pulmonary tuberculosis (38.3% bacteriologically confirmed, 20% clinically confirmed). Fifty five percent participants had CRP level ≥10 mg/l, 83% had ferritin serum level ≥260 ng/ml, and 83% had CD4 cell count<200 cell/ml. Multivariate analysis showed that the most influential factor for PTB in HIV patients was CRP level≥10 mg/l (adjusted prevalence ratio/APR=4.9; 95%CI=7.81-2327,04, p=0.001) and ferritin serum level ≥260 ng/ml (APR=3.32, 95%CI=1.752-433.65, p=0.018).

Conclusions: High CRP and ferritin serum levels were significantly related with PTB in naive HIV patients. No relationship was found between low CD4 cell count and PTB in naive HIV patients.

Author Biography

Ida Bagus Putu Adi Styawan, Department Pulmonology and Respiratory Medicine, Udayana University, Denpasar, Bali, Indonesia

Resident of pulmonology and respiratory medicine study program


WHO. Global Tuberculosis Report, 2020. Available at: Accessed on 13 February 2022.

Winter JR, Stagg HR, Smith CJ, Lalor MK, Davidson JA, Brown AE, et al. Trends in, and factors associated with, HIV infection amongst tuberculosis patients in the era of anti-retroviral therapy: a retrospective study in England, Wales and Northern Ireland. BMC Med. 2018;16(1):85.

Letang E, Ellis J, Naidoo K, Casa EC, Sanchez P, Moosa R. Tuberculosis-HIV Co-Infection: Progress and Challenges After Two Decades of Global Antiretroviral Treatment Roll-Out. Archivos de Bronconeumología. 2020;6(10).

Bell LCK, Noursadeghi M. Pathogenesis of HIV-1 and Mycobacterium tuberculosis co-infection. Nature. 2017;1-11.

Stevens WS, Scott L, Noble L, Gous N, Dheda K. Impact of the GeneXpert MTB/RIF Technology on Tuberculosis Control. Microbiol Spectr. 2017;5(1).

Shapiro AE, Hong T, Govere S, Thulare H, Moosa MY, Dorasamy A, et al. C-reactive protein as a screening test for HIV-associated pulmonary tuberculosis prior to antiretroviral therapy in South Africa. AIDS. 2018;32(13):1811-20.

Yoon C, Chaisson LH, Patel SM, Allen IE, Drain PK, Wilson D, Cattamanchi A. Diagnostic accuracy of C-reactive protein for active pulmonary tuberculosis: a meta-analysis. Int J Tuberc Lung Dis. 2017;21(9):1013-19.

Nakiyingi L, Bwanika JM, Ssengooba W, Mubiru F, Nakanjako D, Joloba ML, et al. Chest X-ray interpretation does not complement Xpert MTB/RIF in diagnosis of smear-negative pulmonary tuberculosis among TB-HIV co-infected adults in a resource-limited setting. BMC Infect Dis. 2021;21(1):63.

Kakoma LN, Mukesi M, Moyo SR. Effectiveness of GeneXpert Technology in the Diagnosis of Smear-Negative Pulmonary Mycobacterium tuberculosis in HIV Positive Patients in Namibia. Open J Med Microbiol. 2016;6:133-41.

Meca AD, Bogdan M, Stiolica A, Cocos R, Ungureanu BJ, Subtirelu MS, et al. Screening Performance of C-Reactive Protein for Active Pulmonary Tuberculosis in HIV-Positive Patients: A Meta-analysis. Res Square. 2017;1-21.

Mishra S, Taparia P, Yadav D, Koolwal S. Study of Iron Metabolism in Pulmonary Tuberculosis Patients. Int J Health Sci Res. 2018;8:70-7.

Opolot JO, Theron AJ, Phail P, Feldman C, Anderson R. Effect of smoking on acute phase reactants, stress hormone responses and vitamin C in pulmonary tuberculosis. Afr Health Sci. 2017;17(2):337-45.

Akpan PA, Okafor IM, Anakebe S. Altered Protein and Iron Levels of Patients With Active Tuberculosis In A Nigerian Reference Health Facility. Afr J Cln Exper Microbiol. 2017;18(3):174-8.

Wilson D, Badri M, Maartens G. Performance of serum C-reactive protein as a screening test for smear-negative tuberculosis in an ambulatory high HIV prevalence population. PLoS One. 2011;6(1):15248.

Foromera J, Paul K, Drain PK, Moosa Y, Plessis C. Diagnostic and prognostic value of ESR and CRP in HIV positive Adults in Durban, South Africa. HMS 2017;1-15.

Drain PK, Mayeza L, Bartman P, Hurtado R, Moodley P, Varghese S, et al. Diagnostic accuracy and clinical role of rapid C-reactive protein testing in HIV-infected individuals with presumed tuberculosis in South Africa. Int J Tuberc Lung Dis. 2014;18(1):20-6.

Visser A, Mostert C. Causes of hyperferritinaemia classified by HIV status in a tertiary-care setting in South Africa. Epidemiol Infect. 2013;141(1):207-11.

Olsson O, Björkman P, Jansson M, Balcha TT, Mulleta D, Yeba H, et al. Plasma Profiles of Inflammatory Markers Associated With Active Tuberculosis in Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Positive Individuals. Open Forum Infect Dis. 2019;6(2):15.

Lawn SD, Kerkhoff AD, Vogt M, Wood R. Diagnostic and prognostic value of serum C-reactive protein for screening for HIV-associated tuberculosis. Int J Tuberc Lung Dis. 2013;17(5):636-43.

Dermid JM, Hennig BJ, Sande M, Hill AV, Whittle HC, Jaye A, et al. Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study. BMC Infect Dis. 2013;13:48.

Negussie A, Debalke D, Belachew T, Tadesse F. Tuberculosis co-infection and its associated factors among People living with HIV/AIDS attending antiretroviral therapy clinic in southern Ethiopia: a facility based retrospective study. BMC Res Notes. 2018;11(1):417.






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