Fig. 1

Diagnosis by nucleic acid amplification test (NAAT). Molecular assays with nucleic acid amplification tests (NAAT) are used for direct detection to improve diagnostic sensitivity. Types of NAAT include polymerase chain reaction (PCR), nested PCR, quantitative PCR, reverse transcriptase PCR, and droplet digital PCR (ddPCR). Notably, nPCR has a higher specificity and sensitivity than conventional PCR, especially in seronegative and serologically different individuals. In addition to blood and cerebrospinal fluid (CSF), scholars have begun to explore other types of specimens, such as tissue or lesional smears, saliva, urine, aqueous humor, semen, amniotic fluid, and placental tissue. NAAT mainly aims at three target genes of T.pallidum, including the DNA polymerase I gene (polA), Tp47(tp0574), and bmp; besides, 16S rRNA, tmpC, subsurface lipoprotein 4D (4D), and tmpA were involved. T. pallidum can be diagnosed in part by targeting its DNA, but mRNA or non-coding RNAs (ncRNAs) can also be targeted for complementary diagnosis