Association of intermediate Nugent Score and bacterial vaginosis with sexually transmitted infections and vulvovaginal candidiasis

Plain Language Summary

This clinical study evaluated the association of bacterial vaginosis and intermediate stage, as per Nugent’s Score, with various sexually transmitted infections and vulvovaginal candidiasis. We observed an incremental increase in the likelihood of acquisition of sexually transmitted infections and vulvovaginal candidiasis with the increase in the abnormality of vaginal flora.

Introduction

Bacterial vaginosis (BV) is a common vaginal syndrome due to the alteration of normal vaginal flora. The vaginal lactobacilli are replaced and dominated by the growth of anaerobes and gram-negative bacteria (Gardnerella vaginalis).¹ This leads to disruption of vaginal microflora resulting in grey or white, thin, and malodorous discharge. Worldwide, the prevalence of bacterial vaginosis varies substantially, ranging from 15 to 49%.^2–5 It has been associated with complications related to women’s reproductive health and contributes to morbidity among females in developing countries. Traditionally, Nugent scoring is used to categorise vaginal flora as bacterial vaginosis normal, intermediate and positive.⁶ Previously, many studies have observed association and increased susceptibility of various sexually transmitted infections (STIs) in BV positive and negative patients.⁷ In a recent systematic review and meta-analysis, a nearly 2-fold higher risk for acquiring Trichomonas vaginalis was observed in bacterial vaginosis-positive patients than in those without bacterial vaginosis.⁸ Also, concurrent vaginal Candida colonization was independently associated with approximately two-fold increased odds for bacterial vaginosis.⁹

Studies on intermediate Nugent Score (BV intermediate) are lacking. There is a growing body of literature that vaginal bacterial communities, like lactobacillus, play a pivotal role in preventing colonization and infection by pathogens causing STIs and vulvovaginal candidiasis. Only a few prospective studies have been assessed to see the association of vaginal microbiota with the incidence of STIs and vulvovaginal candidiasis. However, these studies were conducted among high-risk group females, that is, female sex workers or women attending STIs clinics.^10,11 Most of these studies have observed the relationship between various STIs and vulvovaginal candidiasis between BV positive and negative patients. As known, the increase in the Nugent Score corresponds to the progression in vaginal dysbiosis and decrease in the lactobacillus population.⁶ Bacterial vaginosis intermediate has the propensity to progress towards the BV-positive stage. Thus, it is important to study the association of STIs in the BV positive and BV intermediate categories individually. Therefore, this study was conducted to evaluate the relationship between STIs and vulvovaginal candidiasis among female subjects with negative, intermediate and positive bacterial vaginosis categories individually.

Material and Methods

Results

Characteristics of the study population

The age of females in the present study ranged from 15 to 50 years, with a median age of 28.0 years (interquartile range: 10) [Figure 1]. Based on the Nugent scoring, number of patients with positive, intermediate, and negative scores for BV were 479 (13.6%), 837 (23.7%) and 2215 (62.7%), respectively. Among the subjects with BV, 7.7% (37 of 479) were infected with one of the two sexually transmitted organisms, compared with an infection rate of 6.2% (52 of 837) in patients with BV intermediate and 2.8% (64 of 2215) for subjects without BV.

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Figure 1:

Relation of various categories of Nugent scoring with different age groups

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Association of bacterial vaginosis with vulvovaginal candidiasis

Of all the subjects with BV, 14 (15.4%) women had vulvovaginal candidiasis. The BV patients were 1.2 times more likely to be infected with yeast infection than were subjects without BV (95% confidence interval, 0.850–1.634). The number of vulvovaginal candidiasis cases in both BV intermediate and BV positive was nearly the same (9.3 vs 9.8%). However, the difference in vulvovaginal candidiasis between BV positive and negative groups was not significant (P = 0.336). Figure 2 depicts the distribution of various yeast species among patients with different Nugent scores. Chlamydia trachomatis was the most common yeast isolated overall, followed by Candida glabrata (195 vs 85) [Figure 2]. Other less common yeasts were Chlamydia trachomatis, Candida krusei, Candida kefyr, Candida parapsilosis and Candida lambica.

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Figure 2:

The distribution of various yeast species among patients with different Nugent Scores viz; normal, intermediate and bacterial vaginosis

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Discussion

This study represents a large study population that provides evidence of the association of BV positive and BV intermediate with sexually transmitted infections and vulvovaginal candidiasis. The prevalence of BV in the current study was 13.6%, which is nearly similar to another study from the South India where the prevalence was 15.4%.² However, a higher rate of BV has been reported in various other parts of the world, ranging from 29 to 49%.^3–5

We observed an incremental increase (3.8–5.2%) in the likelihood of acquisition of Trichomonas vaginalis infection with an increase in the abnormality of vaginal flora. Similar findings were also observed by Brotman et al., where the intermediate state was associated with a 1.5–2-fold increased risk for Trichomonas vaginalis infection.¹⁷ These above findings are suggestive that females without BV but with an altered vaginal flora may pose a risk for STIs.²⁴ Although epidemiological data suggest a strong association of Trichomonas vaginalis infection with BV, the prevalence of these infections is probably underestimated since both can be asymptomatic or clinically present with common symptoms of vaginal discharge.¹⁸ Rathod et al. observed a four to nine-fold increased risk of Trichomonas vaginalis infection among sexually active females with abnormal vaginal flora, suggesting a causal role of altered microbiota on trichomonad infection.¹⁹ In in vitro experiments, Hinderfeld and Simoes-Barbosa observed that biofilm produced by dysbiotic bacterias increased the adhesion of the protozoa to host cells. Thus, it is plausible that BV intermediate alters the vaginal ecology and facilitates the acquisition of STIs.

Secondly, we observed a higher number of Mycoplasma hominis cases in the BV intermediate category than BV positive cases (P = 0.002). On the contrary, Cox et al., observed a significantly higher presence of Mycoplasma hominis in BV positive (60.7%) patients compared to BV intermediate and nonbacterial vaginosis (36.4 and 8.8 %, P < 0.001) stages.²⁰ Both the BV positive and BV intermediate stages are characterized by decreased protective lactobacilli.²¹ These findings suggest BV intermediate has unique epidemiology and represents unique taxa of the bacterial community, which needs to be defined by further studies.²¹

Mycoplasma hominis has been found in symptomatic women as well as healthy females. Various studies have observed its association with altered vaginal flora, including BV positive and Trichomonas vaginalis infection. Belkum et al. observed the highest prevalence of Mycoplasma hominis prevalence in the groups of patients infected with Trichomonas vaginalis or those who were BV positive (71 and 38%, respectively).²² This was also observed in the present study, where the maximum number of cases (5 of 6) had concurrent Trichomonas vaginalis and Mycoplasma hominis infection. We did not observe an increase in symptoms once Mycoplasma hominis infection was detected along with Trichomonas vaginalis. However, the question remains elusive, whether in BV, the Trichomonas vaginalis predisposes to Mycoplasma hominis infection or if this is merely an association. In one study, a symbiotic association between Trichomonas vaginalis and Mycoplasma hominis was observed to influence the host-microbes interactions, which is detrimental to their host but beneficial to both microbial partners during infections.²³ However, further research is required to study the association between these STIs.

In the current study, concurrent vaginal Candida colonisation was associated with approximately one-fold increased odds of BV. Although not significant, the higher trend of vulvovaginal candidiasis was present in both BV intermediate and BV positive stages [Table 1]. In India, Rathod and co-workers found a positive association between women clinically diagnosed with BV positive and prevalence of vulvovaginal candidiasis (prevalence bacterial vaginosis: bacterial vaginosis normal 12%:6.5%).²⁴ As both BV positive and vulvovaginal candidiasis have overlapping clinical presentation of vaginal discharge, the misclassification between vulvovaginal candidiasis and clinically defined BV is most likely possible.²⁴ The high prevalence of yeast infection/colonisation in BV intermediate may predispose these females to symptomatic vulvovaginal candidiasis, thus leading to repeated visits to hospitals. Also, a significant number of females who are BV positive have yeast colonisation in the vaginal ecosystem. Hence the failure of symptom resolution in patients with targeted therapy to treat BV can be due to the development of vulvovaginal candidiasis from antibiotic exposure or intrinsic failure of the therapy.²⁵ Thus, the identification of patients with concurrent BV and vulvovaginal candidiasis is important due to a major concern of recurrence of symptoms in patients. Lopez et al., observed concurrent BV and vulvovaginal candidiasis in 34% of cases and 29% of patients had a history of recurrent BV.²⁶ The lack of specificity of clinical signs and symptoms of vaginitis and high rate of recurrence mandate clinical and microbiological examination to determine a specific diagnosis. Failure to appreciate the vulvovaginal candidiasis in BV-positive patients leads to inappropriate therapy and increases the rate of recurrence. In accordance with previous studies, Candida albicans was the most frequently isolated species; however, we also observed a high prevalence rate of nonalbicans Candida species.^27,28 Thus, yeast identification, antifungal susceptibility, and continuous epidemiological surveys to measure changes in species distribution from Candida albicans to non-albicans Candida species are important.

A healthy vaginal microbiome plays a pivotal role in protecting the female genital tract against various STIs and vulvovaginal candidiasis. The alteration of host defence against infection due to a decrease in the protective lactobacillus-deficient environment leads to increased susceptibility to STIs due to the presence of BV associated organisms and their metabolites. Further release of microbial products alters the vaginal microenvironment.

The major strength of the present study is simultaneous reporting of Nugent Score, cultures, and detection of STIs. While most of the previous literature has been majorly defined in high-risk population, our study assessed females presenting for routine health care, thus providing a panoramic view of the STIs in BV intermediate.

Taking this into consideration, future research should focus on whether intervention should be recommended for females who present with BV intermediate stage. The metagenomics and transcriptomics of vaginal flora in healthy and BV females can facilitate our understanding of the interaction of microbial communities. The knowledge of these communities will assist in the development of interventions that can drive the vaginal microbiota toward a healthier state.