1 Kagujje M, et al. BMJ Open 2023;13:e061907. doi:10.1136/bmjopen-2022-061907 Open access Sensitivity and specifcity of CRP and symptom screening as tuberculosis screening tools among HIV-positive and negative outpatients at a primary healthcare facility in Lusaka, Zambia: a prospective cross-sectional study Mary Kagujje , 1 Winnie Mwanza, 1 Paul Somwe, 2 Lophina Chilukutu, 1 Jacob Creswell, 3 Monde Muyoyeta 1 To cite: Kagujje M, Mwanza W, Somwe P, et al. Sensitivity and specifcity of CRP and symptom screening as tuberculosis screening tools among HIV-positive and negative outpatients at a primary healthcare facility in Lusaka, Zambia: a prospective cross- sectional study. BMJ Open 2023;13:e061907. doi:10.1136/ bmjopen-2022-061907 ► Prepublication history for this paper is available online. To view these fles, please visit the journal online (http://dx.doi. org/10.1136/bmjopen-2022- 061907). MK and WM contributed equally. Received 10 February 2022 Accepted 22 March 2023 For numbered affliations see end of article. Correspondence to Dr Mary Kagujje; mkagujje@gmail.com Original research © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. ABSTRACT Objectives To evaluate the performance of point-of- care C-reactive protein (CRP) as a screening tool for tuberculosis (TB) using a threshold of 10 mg/L in both people living with HIV (PLHIV) and HIV-negative individuals and compare it to symptom screening using a composite reference for bacteriological confrmation of TB. Methods Prospective cross-sectional study. Setting A primary healthcare facility in Lusaka, Zambia. Participants Consecutive adults (≥18 years) presenting for routine outpatient healthcare were enrolled. Of the 816 individuals approached to participate in the study, 804 eligible consenting adults were enrolled into the study, of which 783 were included in the analysis. Primary outcome measures Sensitivity, specifcity, positive predictive value and negative predictive value (NPV) of CRP and symptom screening. Results Overall, sensitivity of WHO-recommended four- symptom screen (W4SS) and CRP were 87.2% (80.0–92.5) and 86.6% (79.6–91.8) while specifcity was 30.3% (26.7– 34.1) and 34.8% (31.2–38.6), respectively. Among PLHIV, sensitivity of W4SS and CRP was 92.2% (81.1–97.8) and 94.8% (85.6–98.9) while specifcity was 37.0% (31.3– 43.0) and 27.5% (22.4–33.1), respectively. Among those with CD4≥350, the NPV for CRP was 100% (92.9–100). In the HIV negative, sensitivity of W4SS and CRP was 83.8% (73.4–91.3) and 80.3% (69.5–88.5) while specifcity was 25.4% (20.9–30.2) and 40.5% (35.3–45.6), respectively. Parallel use of CRP and W4SS yielded a sensitivity and NPV of 100% (93.8–100) and 100% (91.6–100) among PLHIV and 93.3% (85.1–97.8) and 90.0% (78.2–96.7) among the HIV negatives, respectively. Conclusion Sensitivity and specifcity of CRP were similar to symptom screening in HIV-positive outpatients. Independent use of CRP offered limited additional beneft in the HIV negative. CRP can independently accurately rule out TB in PLHIV with CD4≥350. Parallel use of CRP and W4SS improves sensitivity irrespective of HIV status and can accurately rule out TB in PLHIV, irrespective of CD4 count. BACKGROUND C-reactive protein (CRP) is one of the biomarkers of tuberculosis (TB) irrespec- tive of HIV status 1–10 ; it is also a biomarker of several other diseases associated with acute or chronic inflammation. 11–16 Among people living with HIV (PLHIV), CRP has a high sensitivity but the specificity is variable depending on the CD4 count, Anti-Retroviral Therapy (ART) status and whether it is used in an inpatient or outpatient setting. 8 17 CRP has a higher specificity among outpatients in comparison to inpatients 2 and among patients with higher CD4 count. 8 Additionally, while very low CRP values exclude active TB, high CRP values are a predictor of mortality. 7 18 There is paucity of literature on utility of CRP for TB screening among HIV-negative indi- viduals and it shows variable sensitivity and specificity of the test. 5 9 10 STRENGTHS AND LIMITATIONS OF THIS STUDY ⇒ Our study included HIV-negative individuals, so it adds to the limited evidence on the utility of C- reactive protein (CRP) in the HIV-negative population. ⇒ We used a composite of culture or Xpert MTB/RIF Ultra as the reference standard, providing an accu- rate reference against which presence or absence of pulmonary tuberculosis (TB) could be defned in routine practice. ⇒ The sample size limits the ability to detect differenc- es in the subpopulation analysis. ⇒ The study population had a high burden of TB, so it is not representative of all populations. ⇒ We did not compare the performance of the CRP threshold of 10 mg/L to that of 5 mg/L used by WHO. on October 30, 2023 by guest. 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