Validasi Uji Polymerase Chain Reaction Multipleks dan Xpert MTB/RIF untuk Deteksi Patogen Penyebab Infeksi Sistem Saraf Pusat

Bardatin Lutfi Aifa, Prof. Dr. dr. Ismail Setyopranoto, Sp.N., Subsp.NIOO(K); dr. Sekar Satiti, Sp.N., Subsp.NKI(K)

2024 | Tesis-Spesialis | S2 Ilmu Penyakit Saraf

Latar belakang: Infeksi sistem saraf pusat (SSP) masih merupakan masalah kesehatan penting di Indonesia dengan moriditas dan mortalitas yang tinggi. Beberapa etiologi utama meliputi Mycobacterium tuberculosis, Streptococcus pneumoniae, Neisseria meningitidis, Cryptococcus species, herpes simplex virus tipe-1 (HSV-1), dan tipe-2 (HSV-2). Uji MTB/RIF Xpert dapat mendeteksi M. tuberculosis pada cairan serebrospinal (CSS) dengan cepat, tetapi memiliki sensitivitas yang rendah. Polymerase chain reaction (PCR) multipleks Biofire® FilmArray® Meningitis/Encephalitis (ME) panel dapat mendeteksi 14 patogen penyebab tersering infeksi SSP, tetapi belum didapatkan penelitian mengenai nilai diagnostiknya di Indonesia.

Tujuan: Melakukan uji diagnostik PCR multipleks Biofire® FilmArray® ME panel dalam mendeteksi S. pneumoniae; N. meningitidis; HSV-1; HSV-2; dan C. neoformans; serta melakukan uji diagnostik Xpert MTB/RIF dalam mendeteksi M. tuberculosis.

Metode: Penelitian ini menggunakan sampel CSS dari pasien dewasa dengan klinis infeksi SSP yang dirawat di RSUP Dr. Sardjito pada September 2022 – Agustus 2023. Sensitivitas / positive percentage of agreement (PPA) dan spesifisitas / negative percentage of agreement (NPA) dari PCR multipleks dan Xpert MTB/RIF dinilai dengan uji pembanding PCR spesifik patogen dan Cryptococcus antigen lateral flow assay.

Hasil: Sebanyak 50 pasien (median usia 35 tahun, 60% laki-laki) disertakan dalam analisis penelitian. Uji Xpert MTB/RIF memiliki PPA 100?n NPA 97,5?lam mendeteksi M. tuberculosis, sedangkan uji PCR multipleks memiliki PPA 100?n NPA 100?lam mendeteksi C. neoformans. Tidak didapatkan sampel yang terdeteksi positif terhadap S. pneumoniae, N. meningitidis, HSV-1, dan HSV-2, sehingga PPA/sensitivitas dan NPA/spesifisitas PCR multipleks dalam mendeteksi patogen tersebut tidak dapat dinilai.

Kesimpulan: Belum didapatkan bukti kebermanfaatan yang bermakna dari PCR multipleks Biofire® FilmArray® ME panel dalam mendeteksi patogen penyebab infeksi SSP di RSUP Dr. Sardjito. Uji Xpert MTB/RIF dapat direkomendasikan sebagai pemeriksaan lini pertama dalam deteksi M. tuberculosis pada CSS dan menjadi acuan diagnosis infeksi tuberkulosis SSP.

Background: Central nervous system (CNS) infection remains a major health problem in Indonesia with high morbidity and mortality. Some of the main etiologies include Mycobacterium tuberculosis, Streptococcus pneumoniae, Neisseria meningitidis, Cryptococcus species, herpes simplex virus type-1 (HSV-1), and type-2 (HSV-2). The MTB/RIF Xpert assay can detect M. tuberculosis in cerebrospinal fluid (CSF) rapidly, however it has low sensitivity. The Biofire® FilmArray® Meningitis/Encephalitis (ME) panel multiplex polymerase chain reaction (PCR) can detect 14 common pathogens causing CNS infections, however its diagnostic value in Indonesia has not been validated.

Objective: To perform diagnostic test on the Biofire® FilmArray® ME panel PCR for the detection of  S. pneumoniae; N. meningitidis; HSV-1; HSV-2; and C. neoformans; and to perform diagnostic test on the Xpert MTB/RIF assay for M. tuberculosis detection.

Methods: This study used CSF samples from adult patients with clinical CNS infections admitted to Dr. Sardjito General Hospital in September 2022 – August 2023. The sensitivity / positive percentage of agreement (PPA) and specificity / negative percentage of agreement (NPA) of multiplex PCR and Xpert MTB/RIF assays were assessed using comparative tests of pathogen-specific PCR and Cryptococcus antigen lateral flow assay.

Results: A total of 50 patients (median age 35 years, 60% male) were included in the study analysis. The Xpert MTB/RIF test had a PPA of 100% and an NPA of 97.5% in detecting M. tuberculosis, while the multiplex PCR test had both PPA and NPA of 100% in detecting C. neoformans. No samples were detected positive for S. pneumoniae, N. meningitidis, HSV-1, and HSV-2, thus the PPA/sensitivity and NPA/specificity of the multiplex PCR in detecting these pathogens were undetermined.

Conclusion: There is no significant evidence of the Biofire® FilmArray® ME panel multiplex PCR efficacy in detecting pathogens causing CNS infections at Dr. Sardjito General Hospital. The Xpert MTB/RIF test could be recommended as a first-line investigation in detecting M. tuberculosis in CSF and as a reference for diagnosing CNS tuberculosis infection.

Kata Kunci : infeksi sistem saraf pusat, meningitis, ensefalitis, PCR multipleks, Xpert MTB/RIF