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