Figure 3 - uploaded by Antonio Carlos Gerbase
Content may be subject to copyright.
Source publication
Sexually transmitted diseases affect millions of people each year and cause considerable disease burden. The Global Burden of Disease Study (GBD) 1990 (1) estimated that over 24 million DALYs were lost due to syphilis, gonorrhoea and chlamydia alone. This chapter presents the methods and results for estimating the global burden of these diseases in...
Citations
... Neisseria gonorrhoeae and Neisseria meningitidis are the only two species that cause disease. These pathogens, which infect only humans, also behave like commensals in that they have a tendency to colonize asymptomatically (18)(19)(20). Commensal Neisseria spp. are little studied, and there are no small animal models for colonization. ...
Commensals are important for the proper functioning of multicellular organisms. How a commensal establishes persistent colonization of its host is little understood. Studies of this aspect of microbe-host interactions are impeded by the absence of an animal model. We have developed a natural small animal model for identifying host and commensal determinants of colonization - and of the elusive process of persistence. Our system couples a commensal bacterium of wild mice, Neisseria musculi , with the laboratory mouse. The pairing of a mouse commensal with its natural host circumvents issues of host restriction. Studies are performed in the absence of antibiotics, hormones, invasive procedures or genetic manipulation of the host. A single dose of N. musculi , administered orally, leads to long-term colonization of the oral cavity and gut. All mice are healthy. Susceptibility to colonization is determined by host genetics and innate immunity. On the part of N. musculi , colonization requires the Type IV pilus. Reagents and powerful tools are readily available for manipulating the lab mouse, allowing easy dissection of host determinants controlling colonization resistance. N. musculi is genetically related to human-dwelling commensal and pathogenic Neisseria and encodes host interaction factors and vaccine antigens of pathogenic Neisseria . Our system provides a natural approach for studying Neisseria -host interactions, and is potentially useful for vaccine efficacy studies.
... A growing number of malignancies are also attributed to STIs, notably cervical, anal and penile cancers as well as hepatocellular carcinoma. Congenital infections in the new-born include congenital syphilis, ophthalmia neonatorum and pneumonia [7,8]. ...
... While gonorrhea is treatable with antibiotics, a large number of infections are asymptomatic, and therefore go untreated. Asymptomatic infections are of particular concern for women; over 60% of women infected with N. gonorrhoeae do not show obvious symptoms of disease (Gerbase et al., 2006). Left untreated, gonorrhea can lead to pelvic inflammatory disease, ectopic pregnancy and infertility (Trigg et al., 2008). ...
Neisseria gonorrhoeae regulates the expression of epithelial cell genes, activates cytoprotective pathways in the infected cell and protects it from apoptosis. Many of these responses are enhanced by the Type IV pilus (Tfp). We tested the hypothesis that N. gonorrhoeae modulates the innate immune response by inducing expression of ATF3, a transcription factor that negatively regulates the expression of many cytokine genes. We further determined whether Tfp are involved in these events. We found that N. gonorrhoeae induces ATF3 expression in mucosal epithelial cells through activation of mitogen activated protein kinases. Maximal ATF3 expression requires Tfp retraction. Knocking down endogenous levels of ATF3 results in higher levels of IL-6 transcript. Our findings strongly suggest that ATF3 is involved in suppressing cytokine expression during gonococcal infection. We propose a model for the role of ATF3 in the context of N. gonorrhoeae infection.
Unlabelled:
Background Despite the availability of testing and treatment, bacterial sexually transmissible infections (STIs) continue to occur at endemic levels in many remote Indigenous communities in Australia. New generation molecular point-of-care (POC) tests have high sensitivity, comparable with conventional diagnostic tests, and have the potential to increase the impact of STI screening.
Methods:
We developed mathematical models of gonorrhoea (Neisseria gonorrhoeae) and chlamydia (Chlamydia trachomatis) transmission in remote Indigenous communities in Australia to evaluate screening and treatment strategies that utilise POC tests.
Results:
The introduction of POC testing with 95% sensitivity could reduce the prevalence of gonorrhoea and chlamydia from 7.1% and 11.9% to 5.7% and 8.9%, respectively, under baseline screening coverage of 44% per year. If screening coverage is increased to 60% per year, prevalence is predicted to be reduced to 3.6% and 6.7%, respectively, under conventional testing, and further reduced to 1.8% and 3.1% with the introduction of POC testing. Increasing screening coverage to 80% per year will result in a reduction in the prevalence of gonorrhoea and chlamydia to 0.6% and 1.5%, respectively, and the virtual elimination of both STIs if POC testing is introduced.
Conclusions:
Modelling suggests that molecular POC tests of high sensitivity have great promise as a public health strategy for controlling chlamydia and gonorrhoea. However, evaluation of the cost-effectiveness of POC testing needs to be made before widespread implementation of this technology can be considered.
