Zika virus infection in the genital tract of non-pregnant females: a systematic review

Abstract

This review provides a general overview on the positivity and persistence of Zika virus (ZIKV) in female genital tract (FGT) of non-pregnant women and animals, as well as in cell cultures, and its influence on FGT health. We performed a systematic review based on the PRISMA statement to identify studies focused on "Zika virus" and "non-pregnant female" in PubMed, Embase, Scopus Scholar and Web of Knowledge databases of full-text papers and abstracts published in English, with no restrictions regarding the initial date of publication, up to August 2019. Our search terms yielded 625 records, that were 108 after removal of duplicates, leaving 517 items for title and abstract reviews. Of these, 475 did not meet the inclusion criteria, leaving 42 records for full-text review and resulting in the exclusion of 6 additional records. The remaining 36 met our inclusion criteria. Variations were observed regarding the presence and persistence of ZIKV in lower and upper genital samples. However, the FGT was the place in which ZIKV RNA has been detected, sometimes for relatively long periods, even after the clearance from blood and urine. In addition to the vagina and cervix, the endometrium, uterus and ovary (oocytes and follicles) could also be involved in persistent ZIKV infections. Further prospective studies are needed to assess the effect of ZIKV on FGT health.

Figure 1. Flowchart of the steps performed in this systematic review.

Figure 2. Schematic representation of the possible role of progesterone in the development of ZIKV infection in the lower genital tract, according to animal studies. The responses of rodent epithelium and cervical vaginal stroma to sex steroids are similar to those of humans. Progesterone induces the diestrus phase of the estrous cycle in rats, which is similar to the luteal phase of the menstrual cycle and pregnancy, in which intermediate epithelial squamous cells (IC) predominate. ZIKV could have a higher affinity for vaginal and ectocervical IC, or the vaginal environment with predominance of IC could favor infection with this virus. BC: basal cells; PC: parabasal cells; SC: superficial cells.