What is the significance of clue cells in a vaginal smear?

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From the Guidelines

Clue cells are a definitive indicator of bacterial vaginosis (BV), a condition characterized by an imbalance of the normal vaginal flora, as evidenced by the presence of these cells on microscopic examination 1. The presence of clue cells is one of the diagnostic criteria for BV, which is a clinical syndrome resulting from the replacement of the normal H2O2-producing Lactobacillus sp. in the vagina with high concentrations of anaerobic bacteria, such as Prevotella sp. and Mobiluncus sp., G. vaginalis, and Mycoplasma hominis. Some key points about clue cells and BV include:

  • Clue cells are vaginal epithelial cells covered with bacteria, typically Gardnerella vaginalis, which gives them a stippled or granular appearance under microscopic examination.
  • The diagnosis of BV can be made using clinical or Gram-stain criteria, with the presence of clue cells being one of the key diagnostic signs, in addition to a homogeneous, white, noninflammatory discharge, a pH of vaginal fluid >4.5, and a fishy odor of vaginal discharge before or after addition of 10% KOH (i.e., the whiff test) 1.
  • Treatment of BV typically involves antibiotics, such as metronidazole or clindamycin, to relieve symptoms and prevent potential complications.
  • It's worth noting that up to 50% of women with BV may not report symptoms, and the condition is associated with having multiple sex partners, douching, and lack of vaginal lactobacilli, although the exact cause of the microbial alteration is not fully understood 1.

From the FDA Drug Label

NOTE: For purposes of this indication, a clinical diagnosis of bacterial vaginosis is usually defined by the presence of a homogeneous vaginal discharge that ... (c) contains clue cells on microscopic examination. The presence of clue cells on microscopic examination is one of the diagnostic criteria for bacterial vaginosis.

  • Clue cells are a key indicator of bacterial vaginosis.
  • They are typically identified through microscopic examination of a vaginal discharge sample. 2

From the Research

Definition of Clue Cells

  • Clue cells are epithelial cells heavily covered with adherent bacteria, and are an accepted clue to the diagnosis of bacterial vaginosis 3.
  • These cells are characterized by the presence of gram-negative rods, specifically Gardnerella vaginalis, adhering to their surface 4.

Diagnosis of Bacterial Vaginosis using Clue Cells

  • The presence of 20% or more clue cells in a Papanicolaou smear is an accurate and reproducible criterion for the diagnosis of bacterial vaginosis 5.
  • Clue cells can be identified through fluorescence in situ hybridization (FISH) and immunofluorescence studies, which can help distinguish between true clue cells and pseudo clue cells 3, 4.

Treatment of Bacterial Vaginosis

  • Clindamycin vaginal ovules and oral metronidazole are effective treatments for bacterial vaginosis, with clue cells being used as a diagnostic criterion to evaluate treatment outcomes 6.
  • A single 1-g oral dose of secnidazole has also been shown to be effective in curing bacterial vaginosis, with a significant reduction in the presence of clue cells and Gardnerella vaginalis 7.

Characteristics of Clue Cells

  • True clue cells are characterized by direct cohesive adherence to epithelial cells, which is unique to Gardnerella species 3.
  • Pseudo clue cells, on the other hand, are formed by the mechanical entrapment of epithelial cells in bacterial masses, and are not specific to Gardnerella species 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Clue Cells and Pseudo Clue Cells in Different Morphotypes of Bacterial Vaginosis.

Frontiers in cellular and infection microbiology, 2022

Research

Low-dose secnidazole in the treatment of bacterial vaginosis.

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 2005

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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