Asymptomatic sexually transmitted diseases: the case for screening

Farley, Thomas A.; Cohen, Deborah A.; Elkins, Whitney L

doi:10.1016/s0091-7435(02)00058-0

Cited by 256 publications

(197 citation statements)

References 23 publications

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“…Nonetheless, asymptomatic carriage of N. meningitidis is of concern as it is the mechanism by which the reservoir of endemic meningococci is maintained within the population. Similarly, asymptomatic gonococcal infection of women plays an important role in maintaining transmission of N. gonorrhoeae (68). Neisserial species other than meningococci also colonize the upper respiratory tract but are classified as part of the normal flora.…”

Section: Table 4 Expression Of Pea (A) O-acetate (B) and Sialic Acimentioning

confidence: 99%

Lipooligosaccharide Structures of Invasive and Carrier Isolates of Neisseria meningitidis Are Correlated with Pathogenicity and Carriage

John

Phillips²,

Din

et al. 2016

Journal of Biological Chemistry

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The degree of phosphorylation and phosphoethanolaminylation of lipid A on neisserial lipooligosaccharide (LOS), a major cell-surface antigen, can be correlated with inflammatory potential and the ability to induce immune tolerance in vitro. On the oligosaccharide of the LOS, the presence of phosphoethanolamine and sialic acid substituents can be correlated with in vitro serum resistance. In this study, we analyzed the structure of the LOS from 40 invasive isolates and 25 isolates from carriers of Neisseria meningitidis without disease. Invasive strains were classified as groups 1-3 that caused meningitis, septicemia without meningitis, and septicemia with meningitis, respectively. Intact LOS was analyzed by high resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Prominent peaks for lipid A fragment ions with three phosphates and one phosphoethanolamine were detected in all LOS analyzed. LOS from groups 2 and 3 had less abundant ions for highly phosphorylated lipid A forms and induced less TNF-␣ in THP-1 monocytic cells compared with LOS from group 1. Lipid A from all invasive strains was hexaacylated, whereas lipid A of 6/25 carrier strains was pentaacylated. There were fewer O-acetyl groups and more phosphoethanolamine and sialic acid substitutions on the oligosaccharide from invasive compared with carrier isolates. Bioinformatic and genomic analysis of LOS biosynthetic genes indicated significant skewing to specific alleles, dependent on the disease outcome. Our results suggest that variable LOS structures have multifaceted effects on homeostatic innate immune responses that have critical impact on the pathophysiology of meningococcal infections.Our previous studies of neisserial lipooligosaccharide (LOS) 2 and the human innate immune system have shown that the degree of phosphorylation of the lipid A component is correlated with the potential of the LOS to induce inflammation stimulated by innate immunity as revealed by cytokine induction in human monocytes in vitro and, in general, with the severity of infections (1-3). In the LOS of Neisseria meningitidis, the modification of lipid A with phosphoethanolamine (PEA) also has been shown to inhibit the bactericidal activity of cathepsin G within neutrophil extracellular traps (4) and to increase adhesion of the bacteria to human cells (5). Expression of PEA on the oligosaccharide (OS) of meningococcal LOS (Fig. 1), particularly in the O-3 position on heptose (Hep) II, or expression of sialic acid (Neu5Ac) have been shown to inhibit activation of complement via the classical and alternative pathways (6 -9). In this study, we postulated that analysis of the structures of the LOS and the genomic diversity of genes for LOS biosynthesis would reveal differences associated with the severity of meningococcal infection and with carrier versus invasive strains of N. meningitidis.To ascertain whether such differences exist, we characterized the structures of LOS from isolates from infected patients or from carriers of N. meningitidi...

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Section: Table 4 Expression Of Pea (A) O-acetate (B) and Sialic Acimentioning

confidence: 99%

Lipooligosaccharide Structures of Invasive and Carrier Isolates of Neisseria meningitidis Are Correlated with Pathogenicity and Carriage

John

Phillips²,

Din

et al. 2016

Journal of Biological Chemistry

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“…For the former, we used the same per partnership transmission probabilities, and durations of infectiousness, as proposed by Garnett et al (1999). However, because clinic-based observations overestimate the proportion of new infections that are symptomatic and care seeking (Farley et al 2003), we used values from a study that estimated this parameter from the combined results of clinic and community-based case-finding methods ( Farley et al 2003). The total number of incident cases (T ) was based on the modelled incidence of symptomatic careseeking infections, divided by an adjustment factor since care-seeking infections account for only a fraction (a j ) of all clinic patients seen (Jungmann et al 2004), i.e.…”

Section: Model Parametersmentioning

confidence: 99%

“…To model chlamydia, we assumed that transmissibility was fairly similar (Lin et al 1998), but that only 9 per cent and 24 per cent of incident male and female infections, respectively, would seek care. These estimates came from the same study from which we obtained the corresponding parameter for gonorrhoea ( Farley et al 2003) and all other parameters were left unchanged. Monteiro and colleagues had previously estimated a Gini coefficient of 0.26 for chlamydia (Monteiro et al 2005).…”

Section: Mp Explanation For Epidemiological Observations About Gonorrmentioning

confidence: 99%

A metapopulation modelling framework for gonorrhoea and other sexually transmitted infections in heterosexual populations

Chen

Ghani

Edmunds

2008

J. R. Soc. Interface.

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Gonorrhoea continues to be a public health problem in the UK, and is the second most common bacterial sexually transmitted infection (STI ) after chlamydia. In the UK, gonorrhoea is disproportionately concentrated in epidemiologically distinct subpopulations, with much higher incidence rates in young people, some ethnic minorities and inner city subpopulations. The original model of STI transmission proposed by Hethcote and Yorke explained some of these features through the concept of the 'core group'. Since then, several authors have modified the original model approach to include multiple sexual activity classes, but found this modelling approach to be inadequate when applied to low-prevalence settings such as the UK. We present a metapopulation framework for modelling gonorrhoea and other STIs. The model proposes that the epidemiology of gonorrhoea is largely driven by subpopulations with higher than average concentrations of individuals with high sexual risk activity. We show how this conceptualization of gonococcal epidemiology overcomes key limitations associated with some of the prior efforts to model gonorrhoea. We also use the model to explain several epidemiological features of gonorrhoea, such as its asymmetric distribution across subpopulations, and the contextual risk experienced by members of at-risk subpopulations. Finally, we extend the model to explain the distribution of other STIs, using chlamydia as an example of a more ubiquitous bacterial STI.

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“…Interestingly, studies in this model revealed several features of infection that mimic a good spectrum of the characteristics of the human disease. Some of them seem highly valuable, (i) the bacteria introduced in the vagina not only invade and colonize the lower genital tract, but also spread to the upper organs (uterus and oviducts) , (ii) infection occurs with no signs of the disease, just as it occurs in a high percentage of women during natural infection (Farley et al, 2003;Inaba et al, 1992) and (iii) the bacteria remains alive within the internal compartments of the infected cells, invading uterine tissues up to 22 days post inoculation (Imarai et al, 2008).…”

Section: N Gonorrhoeae Mice Infectionmentioning

confidence: 99%

“…Ocular infections also occur, and in neonates could cause blindness (Tapsall, 2001). Genital infection in men usually causes urethritis and epididimitis with purulent urethral exudates (Apicella et al, 1996), however an important proportion of infected men never develop symptoms and more than half of infected women develop an asymptomatic silent infection (Farley et al, 2003;Handsfield et al, 1974;John and Donald, 1978). Genital tract gonorrhea gives rise to well recognized complications including upper reproductive tract infections in women, such as pelvic inflammatory disease (PID), a condition that affects between 10% and 20% of infected women in the third world.…”

Section: Introductionmentioning

confidence: 99%