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Bacterial vaginosis (BV) has been reported in one-third of women worldwide at different life stages, due to the complex balance in the ecology of the vaginal microbiota. It is a common cause of abnormal vaginal discharge and is associated with other health issues. Since the first description of anaerobic microbes associated with BV like Gardnerella vaginalis in the 1950s, researchers have stepped up the game by incorporating advanced molecular tools to monitor and evaluate the extent of dysbiosis within the vaginal microbiome, particularly on how specific microbial population changes compared to a healthy state. Moreover, treatment failure and BV recurrence rate remain high despite the standard antibiotic treatment. Consequently, researchers have been probing into alternative or adjunct treatments, including probiotics or even vaginal microbiota transplants, to ensure successful treatment outcomes and reduce the colonization by pathogenic microbes of the female reproductive tract.
2. Pathogenesis of BV and the Identification of Causative Agents
3. Diagnostics Methods of BV
Vaginal cultures for BV diagnosis generally lack positive predictive value or diagnostic value as the infection itself usually is polymicrobial in nature . Also, bearing in mind that performing conventional bacteria culture can be challenging to observe fastidious microbes and is time-consuming, resulting in misinterpretation or underdiagnosis. One of the standard methods for clinical diagnosis of BV is based on the presence of three out of four Amsel’s criteria in most clinical settings (Table 1) . The four Amsel’s criteria include: (a) presence of thin grayish-white homogenous discharge, (b) vaginal pH above 4.5, (c) potassium hydroxide (KOH) test (which is also known as the positive whiff-amine test), and (d) at least 20% clue cells (which are exfoliated vaginal epithelial cells heavily coated with the less favorable microbes) can be observed on a saline wet mount . Alternatively, two other methods can be used to diagnose BV—the Spiegel criteria and Nugent’s criteria. The only similarity between the three tests is the investigation of vaginal smears, though as to the interpretation process, Spiegel’s criteria and Nugent’s criteria focus on morphological observation of microbial cells without considering the presence of clue cells . The Nugent’s criteria, also known as the Gram stain diagnosis method, is considered the gold standard for diagnosing BV based on a 10-point scale using microscopic observation of Gram-stained vaginal smears under the oil immersion method . The score is given as a weighted score calculated from the average number of different morphotypes seen per oil immersion field. Usually, there are three morphotypes described: Lactobacillus spp. morphotype (decrease in number scored as 0 to 4), Gardnerella or Bacteroides spp. morphotype (small gram-variable rods or gram-negative rods; scored as 0 to 4), and curved Gram-variable rods (scored as 0 to 2). The BV diagnosis is confirmed with a score of ≥7; a scoring of 4–6 indicates intermediate flora, and a score of 0–3 is classified as normal flora. Essentially, the scoring system of Nugent’s criteria is derived from the Spiegel criteria, which was described in the early 1980s. However, the Nugent’s criteria present as a better, standardized scoring system with higher intercenter reliability (r = 0.82) than Spiegel criteria (r = 0.61), which led to its adoption as the gold standard for the diagnosis of BV. Additionally, the results from a study by Moussavi and Behrouzi sparked the discussion on whether Amsel’s or Nugent’s criteria are superior to another. The duo studied the sensitivity and specificity of each criterion of Amsel before comparing it to the Nugent’s criteria . Using pH criteria alone showed the lowest sensitivity (61%), while the presence of vaginal discharge alone showed moderate sensitivity (63%) with the highest specificity (80%) among all four criteria when evaluated individually for BV. Equally, the examination of clue cells alone also reflected low sensitivity (67%). Altogether, these findings indicated that the use of tests in Amsel’s criteria showed lower diagnostic validity when used alone compared to Nugent’s criteria, hence further strengthening the need of fulfilling three of the four described criteria described by Amsel et al. for the diagnosis of BV . The Nugent’s criteria versus Amsel’s criteria have comparable diagnostic value for BV as discussed by many research groups, with specificity and sensitivity of Amsel’s criteria reaching as high as 95.2% and 91%, respectively, when compared with Nugent’s criteria . As the Nugent’s criteria require proper laboratory equipment and experienced technical staff, several studies highlighted that Amsel’s criteria could be used to diagnose BV to ensure patients receive the necessary treatment promptly . At the same time, there is another simpler classification known as Hay/Ison criteria, which classified vaginal microbiome into three different categories: normal (Group 1), intermediate (Group 2), and BV (Group 3), depending on the relative amount of Lactobacillus morphotypes as compared to Gardnerella morphotypes . During the first introduction of this classification, Ison and Hay successfully diagnosed BV in 83 out of 162 patients, and the method showed high sensitivity (97.5%), specificity (96%), and predictive value for a positive (94.1%) and negative (96%) test, kappa index = 0.91, when compared with the Amsel’s criteria. A few years later, Chawla et al.’s report also compared Hay/Ison classification and Nugent’s criteria . Their analysis successfully diagnosed 70 BV cases (32.86%) by Nugent’s method and 87 (40.85%) BV cases by Hay/Ison classification. Based on their calculation, Hay/Ison classification’s sensitivity and specificity were determined as ≥97.2% and ≥88.1%, respectively. Collectively, these results implied the suitability of the Hay/Ison classification to be utilized as an alternative diagnosis method when there is a lack of time or expertise . A team in Italy also suggested the potential of automation using the WASP® automatic system (BioMérieux diagnostics) to analyze samples collected in LMB ESwab® (BioMérieux diagnostics). The introduction of advanced technology helps increase reliability and shorten sampling time while ensuring timely diagnosis and treatment .
Table 1. Comparison between Amsel’s, Nugent’s, and Hay/Ison criteria (BV: bacterial vaginosis) (Adapted from Hainer and Gibson ).
Clinical and laboratory diagnosis
Experienced laboratory technicians and pathologist
Experienced laboratory technicians
Diagnosis is confirmed when three out of four criteria are fulfilled.
(a) presence of thin grayish-white homogenous discharge
(b) vaginal pH > 4.5
(c) potassium hydroxide (KOH) or the positive whiff-amine test
(d) at least 20% clue cells observed on a saline wet mount
Score 0 – 4: Normal flora
Score 4 – 6: Intermediate
Score ≥7: BV
Group 1: Normal flora (Lactobacillus only)
Group 2: Intermediate (Lactobacilli = Gardnerella)
Group 3: BV (Lactobacilli < Gardnerella)
Besides using Amsel’s criteria as a point-of-care test, there are other commercially available diagnostic kits for BV . The OSOM BV Blue test (SEKISUI Diagnostics, MA, USA) is a rapid chromogenic diagnostic kit based on bacterial enzyme activity, sialidase . Bypassing the need for laboratory equipment and experts for the interpretation of wet mount, the detection of sialidase activity is simple–placing the vaginal swab into the BV test vessel and mixing gently before adding the developing solution as indicated by the manufacturer’s instructions . Another optional diagnostic kit that would be used is the FemExam card (developed initially by Litmus Concepts, Santa Clara, CA, USA, now available from Cooper Surgical, Shelton, Conn) . The kit comprises two cards: card 1 for pH and amines and card 2 for proline iminopeptidase (PIP) activity. The easy-to-understand feature makes it an attractive diagnostic kit; two swabs are provided with the kit, and each caters for one card. The vaginal fluid collected with the first cotton swab should be applied onto the pH test site and amine test within 2 min to induce a colorimetric reaction. A blue sign on each site indicates a pH of 4.7 or greater and the presence of trimethylamine. Another swab containing vaginal fluid is used on card 2 containing a G. vaginalis PIP activity test site. In the presence of PIP, enzymatic and colorimetric reactions would take place after rubbing the swab onto the test site containing a chromogen (Fast Red) and a PIP substrate (l-propyl-β-naphthylamide). A PIP-positive sample results in a pink color change on the swab tip within 5 min of the test. Although this kit does offer high sensitivity and specificity as compared to conventional clinical diagnosis, the FemExam two-card method comes at a high cost as West et al. estimated the cost per patient and cost per true case detected at US $8.32 and US $18.49, respectively . Lowering the cost for these kits may improve the accessibility in developing countries or even allow its usage as home self-examination using kits, but it remains controversial due to the possible overdiagnosis .
The entry is from 10.3390/antibiotics10060719
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