7.3.1. Molecular detection

NAAT is the current gold standard for detecting C. trachomatis and N. gonorrhoeae among men and women. NAAT also performs well for pharyngeal and anorectal samples for C. trachomatis and N. gonorrhoeae. For anorectal samples among men who have sex with men, chlamydia genovar testing for lymphogranuloma venereum should be done to guide the appropriate treatment regimen for lymphogranuloma venereum (48).

7.3.2. Culture methods

Culture of N. gonorrhoeae is still the standard method for performing antimicrobial susceptibility testing. However, this organism is not that easy to grow in the laboratory, requiring special training and a special culture medium. For this reason, culture of N. gonorrhoeae is not routinely performed as part of managing people with gonococcal infection in resource-limited settings.

Culture of T. vaginalis was the cornerstone for detecting T. vaginalis before the advent of point-of-care antigen tests and NAAT. Although a culture medium is commercially available, once inoculated into the medium, cultures from men have to be incubated for a full five days while being examined daily using a microscope before being determined to be negative. Further, multiple sites, including semen, urine and urethral swabs, need to be examined before a definitive negative result can be certain. Routine culture methods for detecting T. vaginalis are no longer widely performed.

7.3.3. Microscopy

N. gonorrhoeae can be identified by light microscopy of Gram-stained samples and a presumptive diagnosis of gonorrhoea made if gram-negative diplococci are observed intracellularly in polymorphonuclear leukocytes, best seen when there is a urethral discharge. If carried out by an experienced person, a negative gram stain for intracellular diplococci, in the context of urethral discharge in a man, can be presumed to suggest non-gonococcal urethritis. Microscopy of methylene blue stain of a male urethral sample is an acceptable method for the presumptive diagnosis of gonorrhoea, but it does not allow for the differentiation of gram-negative cocci.

7.4.1. Evidence summary (Annex 3)

A systematic review of the accuracy of syndromic approaches for urethral discharge was conducted, including history, risk assessment, examination and microscopy (supplementary material: systematic review urethral discharge). Six studies were found for assessing the accuracy of syndromic management to detect N. gonorrhoeae and C. trachomatis, but the pooled sensitivity and specificity of the approaches did not improve as expected when adding microscopy (low-certainty evidence). In addition, studies show that there is variability in the implementation of the syndromic approaches based on symptoms or laboratory testing (49). Instead, the WHO Guideline Development Group considered that, when available, performing molecular assay tests for N. gonorrhoeae, C. trachomatis, T. vaginalis and/or M. genitalium and basing treatment on these results leads to treating the most people correctly. In the systematic review, the median prevalence of N. gonorrhoeae and/or C. trachomatis was 69% in men with urethral discharge. In a population with 60% prevalence of N. gonorrhoeae and C. trachomatis among those with urethral discharge, if molecular assays are not available, treating everyone for N. gonorrhoeae and C. trachomatis would mean 40% of them would be unnecessarily treated. The Guideline Development Group agreed that this proportion is acceptable and even higher proportions in settings with lower prevalence, because treating everyone would ensure that people infected with N. gonorrhoeae and C. trachomatis are treated, thereby reducing the chance of complications and further transmission. The Guideline Development Group also agreed that simple syndromic treatment based on the presence of urethral discharge would likely improve adherence to the approach and costs a minimal amount more than using history and/or risk assessment with or without examination (but with no missed cases).